Humalog

B - PACKAGE LEAFLET

Package leaflet: Information for the user

Humalog 100 units/ml injectable solution in vial

insulin lispro
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Humalog is and what it is used for

Humalog is used in the treatment of diabetes. Humalog acts more rapidly than regular human insulin due to a small modification of the insulin molecule.
Your condition, diabetes, is caused by your pancreas not producing enough insulin to properly control blood glucose levels. Humalog replaces the insulin your body normally produces and is used to control glucose levels in the long term. The medicine acts very quickly and has a shorter duration of action compared to soluble insulin (from 2 to 5 hours). Normally, you should inject Humalog within 15 minutes before a meal.
Your doctor may prescribe both Humalog and a long-acting insulin. Each type of insulin comes with its own package leaflet containing information on proper use. Do not change the type of insulin unless instructed by your doctor. Exercise great care when switching from one type of insulin to another.
Humalog can be used in both adults and children.

2. What you need to know before using Humalog

DO NOT use Humalog

• If you think you are experiencing hypoglycaemia (low blood sugar level). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section 3: If you use more Humalog than you should).
• If you are allergic to insulin lispro or to any of the excipients in this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and label of the vial to confirm the name and type of insulin provided by your pharmacist. Make sure that your Humalog pack corresponds to the one prescribed by your doctor.

• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet. You must pay careful attention to meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar levels frequently.

• Some people who experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.

• Inform your doctor, pharmacist or diabetes care nurse if you answer YES to any of the following questions:

  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?

• Your insulin requirements may change if you consume alcohol.

• Also inform your doctor, pharmacist or diabetes care nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal schedules compared to your routine at home.

• Some patients with longstanding type 2 diabetes and a history of heart disease or previous cerebrovascular events who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (oedema).

Skin changes at the injection site
You should rotate your injection sites to prevent skin changes such as the development of lumps under the skin. Insulin may not work as effectively if you inject into an area with lumps (see section "How to use Humalog"). If you currently inject into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

Other medicines and Humalog
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemics,
• acetylsalicylic acid,
• sulphonamide antibiotics,
• octreotide,
• beta2-agonists (e.g. ritodrine, salbutamol, terbutaline),
• beta-blockers,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g. captopril, enalapril), and
• angiotensin II receptor antagonists.

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

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements usually decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be impaired if you experience hypoglycaemia. Consider this possibility in any situation where you could endanger yourself or others (e.g. driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia
• have reduced or absent warning signs of hypoglycaemia

Humalog contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. essentially "sodium-free".

3. How to use Humalog

Always use Humalog exactly as your doctor has instructed. If you have any doubts, consult your doctor.

Dose

• Normally, you should inject Humalog within 15 minutes before a meal. If necessary, you may also inject it immediately after a meal. Follow your doctor’s instructions exactly regarding dose, timing, and frequency of administration—these instructions are specific to you. Follow them precisely and have your condition monitored regularly at the diabetes care center.
• If you switch from another type of insulin (for example, from animal or human insulin to a Humalog product), you may require a different dose (higher or lower) than before. This change may occur with the very first injection, or it may be introduced gradually over several weeks or months.
• Inject Humalog subcutaneously. Only inject it intramuscularly if specifically instructed by your doctor.

Preparing Humalog

• Humalog is already dissolved in water, so you must not mix it. However, make sure to use it only if it appears identical to water. The solution must be clear, colourless, and free from solid particles. Check this before each injection.

Injecting Humalog

• First, wash your hands.
• Before injecting, disinfect the skin according to the instructions you have received. Disinfect the rubber stopper of the vial, but do not remove it.
• Use a sterile syringe and needle to pierce the rubber stopper and draw up the required dose of Humalog. Your doctor or diabetes care center will show you exactly how to do this. Never share syringes or needles with other people.
• Inject the medicine subcutaneously as you have been taught. Do not inject it directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure each injection site is at least one centimetre away from the previous one, and remember to rotate injection sites as instructed. It does not matter whether you use the upper arms, thighs, buttocks, or abdomen—the action of Humalog will still be faster than that of soluble human insulin.
• Your doctor will tell you if you need to mix Humalog with one of the human insulins. For example, if you need to inject a mixture, draw Humalog into the syringe first, before drawing up the long-acting insulin. Inject the mixture immediately after preparation. Repeat the same procedure each time. Normally, you should not mix Humalog with pre-mixed human insulins. Never mix Humalog with insulins from other manufacturers or with animal insulins.

Use of Humalog in an insulin pump

• Only certain CE-marked insulin pumps are suitable for delivering insulin lispro. Before administering insulin lispro, carefully read the manufacturer’s instructions to determine whether a specific pump is suitable. Read and follow the instructions provided in the documentation accompanying the insulin pump.
• Make sure you use the correct reservoir and catheter for your insulin pump.
• The infusion set (tubing and needle) must be changed according to the instructions provided with the infusion set.
• If you experience an episode of hypoglycaemia, stop the infusion until the episode has resolved. If you experience repeated or severe episodes of low blood sugar, inform your doctor and consider whether insulin infusion needs to be reduced or stopped.
• A malfunction of the insulin pump or blockage of the infusion set may lead to a rapid rise in blood glucose levels. If you suspect an interruption in insulin flow, follow the instructions in the product documentation and, if appropriate, inform your doctor.
• When used with an insulin pump, Humalog must not be mixed with any other insulin.

If you use more Humalog than you should
If you use more Humalog than prescribed, or if you are unsure of the dose you injected, your blood sugar level may drop. Check your blood sugar level.
If your blood sugar is low (mild hypoglycaemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat some fruit, biscuits, or a sandwich, as advised by your doctor, and rest. This is often sufficient to counteract mild hypoglycaemia or a minor overdose of insulin. If you notice your condition worsening, with shortness of breath and pale skin, contact your doctor immediately. A glucagon injection may be used to treat more severe hypoglycaemia. Take glucose or sugar after receiving a glucagon injection. If you do not respond to glucagon, you must be admitted to hospital. Ask your doctor for information on how to use glucagon.

If you forget to use Humalog
If you use less Humalog than required, or if you are unsure of the dose you injected, your blood sugar level may rise. Check your blood sugar level.
Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see sections A and B of section 4, “Possible side effects”).

Three simple precautions to avoid episodes of hypoglycaemia or hyperglycaemia:

• Always keep spare syringes and a vial of Humalog available.
• Always carry identification indicating that you are diabetic.
• Always carry sugar with you.

If you stop using Humalog
If you use less Humalog than required, your blood sugar level may rise. Do not change the type of insulin you are using unless instructed by your doctor.
If you have any doubts about using this medicine, consult 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 (from ≥ 1/10,000 to <1/1,000). Symptoms include:
rash over the whole body
lowering of blood pressure
difficulty breathing
rapid heartbeat
shortness of breath
sweating
If you think Humalog is causing you this type of insulin allergy, inform your doctor immediately.
Local allergy is common (from ≥ 1/100 to <1/10). In some people, the skin at the injection site may become red, swollen and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is uncommon (from ≥ 1/1,000 to <1/100). If you inject insulin too often in the same spot, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin may also be caused by the build-up of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as well as it should if you inject into an area with lumps. Change your injection site with each injection to prevent these skin changes.
Oedema (e.g. swelling of the arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving glycaemic control.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

Common diabetes-related problems

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means that there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• an overdose of Humalog or another insulin;
• a delayed or missed meal, or a change in diet;
• excessive physical exercise or work performed immediately before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• a change in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycaemia appear rapidly and include:
tiredness
rapid heartbeat
nervousness or restlessness
malaise
headache
cold sweat
If you are unable to recognize the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means that there is not enough insulin in your body. Hyperglycaemia may be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower dose of insulin than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:
drowsiness
loss of appetite
flushed face
fruity odour on the breath
thirst
feeling or showing signs of illness
Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical assistance.

C. Illness
If you are ill, especially if you feel unwell or are sick, your insulin requirements may change. Even when you are not eating normally, you still need insulin. Test your urine and blood; follow the precautions you already know when you are ill, and inform your doctor.

5. How to store Humalog

Before use, store Humalog in the refrigerator (2°C - 8°C). Do not freeze.
During use, store the vial in the refrigerator (2°C - 8°C) or at room temperature (below 30°C) and discard after 28 days. Do not place near heat sources or direct sunlight.
Keep out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers to the last day of the month.
Do not use this medicine if you notice it is discolored or contains solid particles. You should use it only if its appearance is like that of water. Check this carefully before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Humalog 100 units/ml injectable solution contains

• The active substance is insulin lispro. Insulin lispro is produced in the laboratory using a technology called "recombinant DNA technology". It is a modified form of human insulin and is therefore different from other insulins of human or animal origin. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas.
• The excipients are m-cresol, glycerol, disodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may be added to adjust the pH.

Description of the appearance of Humalog and the contents of the pack
Humalog 100 units/ml injectable solution is a sterile, clear, colourless aqueous solution and contains 100 units of insulin lispro per millilitre (100 units/ml) of injectable solution. Each vial contains 1,000 units (10 millilitres). Humalog 100 units/ml injectable solution in vials is available in packs containing 1 vial, 2 vials, or in a multiple pack containing 5 packs of 1 vial each. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Humalog 100 units/ml injectable solution in vials is manufactured by:

• Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain.

The marketing authorisation is held by Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands.
For further information about this medicinal product, please contact the local representative of the marketing authorisation holder.

Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: +32-(0)2 548 84 84 Tel: +370 (5) 2649600

България Luxembourg/Luxemburg
TP "Eli Lilly Nederland" B.V. - Bulgaria Eli Lilly Benelux S.A./N.V.
tel: +359 2 491 41 40 Tél/Tel: +32-(0)2 548 84 84

Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: +420 234 664 111 Tel: +36 1 328 5100

Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: +356 25600 500

Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel: +49-(0)6172 273 2222 Tel: +31-(0)30 60 25 800

Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: +372 6817 280 Tlf: +47 22 88 18 00

Ελλάδα Österreich
FARMASERV-LILLY Α.Ε.Β.Ε. Eli Lilly Ges.m.b.H.
Τηλ: +30 210 629 4600 Tel: +43-(0)1 711 780

España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: +34-91 663 50 00 Tel: +48 22 440 33 00

France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0)1 55 49 34 34 Tel: +351-21-4126600

Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: +40 21 4023000

Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: +353-(0)1 661 4377 Tel: +386 (0)1 580 00 10

Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími: +354 540 8000 Tel: +421 220 663 111

Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: +39-055 42571 Puh/Tel: +358-(0)9 85 45 250

Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Τηλ: +357 22 715000 Tel: +46-(0)8 7378800

Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: +371 67364000 Tel: +44-(0)1256 315000

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

Package leaflet: Information for the user

Humalog 100 units/ml solution for injection in cartridge

insulin lispro
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Humalog is and what it is used for

Humalog is used in the treatment of diabetes. Humalog acts more rapidly than regular human insulin due to a minor modification of the insulin molecule.
Your condition, diabetes, arises because your pancreas does not produce sufficient insulin to control blood glucose levels. Humalog replaces the insulin normally produced by your body and is used to control glucose levels over the long term. The medicine acts very quickly and has a shorter duration of action compared to soluble insulin (from 2 to 5 hours). You should normally inject Humalog within 15 minutes before a meal.
Your doctor may prescribe Humalog together with a long-acting insulin. Each type of insulin comes with its own package leaflet containing information on its proper use. Do not change the type of insulin unless instructed by your doctor. Exercise great care when switching from one type of insulin to another.
Humalog can be used in both adults and children.

2. What you need to know before using Humalog

Do NOT use Humalog

• If you think you are experiencing hypoglycaemia (low blood sugar level). Instructions on how to manage mild hypoglycaemia are provided later in this leaflet (see section 3: If you use more Humalog than you should).
• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and the label on the cartridge to confirm the name and type of insulin dispensed to you by the pharmacist. Make sure that your Humalog pack corresponds to the one prescribed by your doctor.
• If your blood glucose level is well controlled with your current insulin therapy, you may no longer notice the warning symptoms when your blood sugar level is dropping too low. These warning signs are listed later in this leaflet. You must pay close attention to meal times, frequency and intensity of physical exercise, and monitor your blood sugar levels regularly.
• Some people who experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less pronounced or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• Inform your doctor, pharmacist, or diabetes nurse if you answer YES to any of the following questions:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
• Your insulin requirements may change if you consume alcohol.
• Also inform your doctor, pharmacist, or diabetes nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal schedules compared to your routine at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of cerebrovascular events who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).

Skin changes at the injection site
Rotate your injection sites to prevent skin changes such as the formation of lumps under the skin. Insulin may not work as effectively if injected into an area with lumps (see section "How to use Humalog"). If you are currently injecting into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

Other medicines and Humalog
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemic agents,
• acetylsalicylic acid,
• sulfonamide antibiotics,
• octreotide,
• beta2-agonists (e.g., ritodrine, salbutamol, terbutaline),
• beta-blockers,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril), and
• angiotensin II receptor antagonists.

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

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be reduced during a hypoglycaemic reaction. Consider this possibility in any situation where you or others could be at risk (e.g., driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you:

• frequently experience episodes of hypoglycaemia, or
• have reduced or absent warning signs of hypoglycaemia.

Humalog contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially "sodium-free".

3. How to use Humalog

The 3 ml cartridge must only be used with 3 ml Lilly pens. Do not use with 1.5 ml pens.
Always use Humalog exactly as prescribed by your doctor. If you have any doubts, consult your doctor. To prevent possible transmission of disease, each cartridge must be used by only one patient, even if the needle attached to the delivery device is changed.

Dose

• Normally, you should inject Humalog within 15 minutes before a meal. If necessary, you may administer the injection immediately after the meal. Follow your doctor’s instructions precisely regarding dosage, timing, and frequency of administration—these are specific to you. Adhere strictly to these instructions and have regular check-ups at your diabetes care center.
• If you switch from another type of insulin (e.g., animal or human insulin) to a Humalog product, you may require a different dose (higher or lower) than before. This change may occur with the first injection or may be gradually adjusted over several weeks or months.
• Inject Humalog subcutaneously. Only inject it intramuscularly if specifically instructed to do so by your doctor.

Preparation of Humalog

• Humalog is already dissolved in water and must not be mixed. However, use it only if it appears like water. The solution must be clear, colorless, and free of solid particles. Check this before each injection.

Preparing the pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• You must use Humalog cartridges only with Lilly insulin pens. Ensure that the words Humalog or Lilly cartridges are mentioned in the leaflet accompanying your pen. The 3 ml cartridge can only be used with a 3 ml pen.
• Follow the instructions provided with your pen. Insert the cartridge into the pen.
• Set the dose to 1 or 2 units. Hold the pen with the attached needle pointing upward and gently tap the side to dislodge air bubbles. With the pen still pointing upward, press the injection button until a drop of Humalog appears at the needle tip. Small air bubbles may remain in the pen; these are not dangerous, but if they are too large, they may affect the accuracy of the dose.

Injecting Humalog

• Before injecting, disinfect the skin as instructed. Inject the medication subcutaneously as you have been taught. Do not inject directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure each new injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed. It does not matter which site you use—the upper arms, thighs, buttocks, or abdomen—as Humalog will act even more rapidly than soluble human insulin.
• Do not administer Humalog intravenously. Inject Humalog only as taught by your doctor or nurse. Only a doctor may administer Humalog intravenously, and only under special circumstances such as surgery or if you are ill and your blood glucose levels are too high.

After injection

• Immediately after completing the injection, remove the needle from the pen using the outer needle cap. This helps keep Humalog sterile, prevents leakage of the medication, stops air from entering the pen, and prevents needle blockage. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen. Leave the cartridge inside the pen.

Subsequent injections

• Before each subsequent injection, select 1 or 2 units and press the injection mechanism while holding the pen upright until a drop of Humalog appears from the needle. You can estimate how much Humalog remains in the cartridge by observing the level on its side. The distance between each mark corresponds to approximately 20 units. If there is not enough remaining for your next dose, replace the cartridge.

Do not mix any other insulin into the Humalog cartridge. Once the cartridge is empty, do not reuse it.

Use of Humalog in an insulin pump

• Only certain CE-marked insulin pumps are suitable for administering insulin lispro. Before using insulin lispro, carefully read the manufacturer’s instructions to determine whether your specific pump is appropriate. Read and follow the instructions provided in the documentation accompanying the insulin pump.
• Make sure to use the correct reservoir and tubing suitable for your insulin pump.
• The infusion set (tubing and needle) must be changed according to the instructions provided with the infusion set.
• In the event of hypoglycemia, stop the infusion until the episode resolves. If you experience repeated or severe episodes of low blood glucose, inform your doctor and consider whether insulin infusion needs to be reduced or stopped.
• Malfunction of the insulin pump or blockage of the infusion set may lead to a rapid rise in blood glucose levels. If you suspect an interruption in insulin flow, follow the instructions in the product documentation and, if necessary, inform your doctor.
• When used with an insulin pump, Humalog must not be mixed with any other insulin.

If you use more Humalog than you should
If you use more Humalog than prescribed or are unsure of the amount injected, your blood sugar level may drop. Check your blood glucose level. If your blood sugar is low (mild hypoglycemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich as advised by your doctor, and rest. This is often sufficient to counteract mild hypoglycemia or a minor insulin overdose. If your condition worsens and you experience shortness of breath or pale skin, contact your doctor immediately. A glucagon injection can treat more severe hypoglycemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information on how to use glucagon.

If you forget to use Humalog
If you use less Humalog than needed or are unsure of the amount injected, your blood sugar level may rise. Check your blood glucose level. Untreated hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see sections A and B of section 4 “Possible side effects”).

Three simple precautions to avoid episodes of hypoglycemia or hyperglycemia:

• Always keep spare syringes and a vial of Humalog, or a spare pen and cartridges, in case you lose or damage your pen or cartridges.
• Always carry identification indicating that you are diabetic.
• Always carry sugar with you.

If you stop using Humalog
If you use less Humalog than required, your blood sugar level may rise. Do not change the type of insulin you are using unless instructed by your doctor.
If you have any questions about using this product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody experiences them.
Systemic allergy is rare (from ≥ 1/10,000 to <1/1,000). Symptoms include:
rash over the entire body - low blood pressure
- difficulty breathing - rapid heartbeat
- shortness of breath - sweating

If you think Humalog is causing you this type of insulin allergy, inform your doctor immediately.
Local allergy is common (from ≥ 1/100 to <1/10). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is not common (from ≥ 1/1,000 to <1/100). If you inject insulin too often in the same spot, the fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as effectively if injected into an area with lumps. Change the injection site with each injection to prevent these skin changes.
Edema (e.g., swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving glycaemic control.

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

Common diabetes-related problems

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• an overdose of Humalog or another insulin;
• delayed or missed meals, or changes in diet;
• excessive physical exercise or work performed shortly before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• changes in insulin requirements;
• worsening of pre-existing kidney or liver disease.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycaemia appear rapidly and include:
- fatigue - rapid heartbeat
- nervousness or restlessness - malaise
- headache - cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycaemia may be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:
- drowsiness - loss of appetite
- flushed face - fruity odour on breath
- thirst - feeling or signs of malaise

Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical assistance.

C. Illness
If you are ill, especially if you feel unwell or are sick, your insulin requirements may change. Even if you are not eating normally, you still need insulin. Test your urine and blood; when sick, follow the precautions you already know and inform your doctor.

5. How to store Humalog

Before use, store Humalog in the refrigerator (2°C - 8°C). Do not freeze.
During use, store the cartridge at room temperature (below 30°C) and discard it after 28 days. Do not place the product near a heat source or direct sunlight. Do not refrigerate the pen or cartridges in use. The pen containing the cartridge must not be stored with the needle attached.
Keep out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers to the last day of the month.
Do not use this medicine if you notice it is coloured or contains solid particles. You should use it only if its appearance is like that of water. Check this before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Humalog 100 units/ml cartridge solution contains

• The active substance is insulin lispro. Insulin lispro is produced in the laboratory using a technology called recombinant DNA technology. It is a modified form of human insulin and is therefore different from other human or animal insulins. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas.
• The excipients are m-cresol, glycerol, disodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may be added to adjust the pH.

Description of the appearance of Humalog and contents of the pack
Humalog 100 units/ml solution for injection is a sterile, clear, colourless aqueous solution and contains 100 units of insulin lispro per millilitre (100 units/ml) of injectable solution. Each cartridge contains 300 units (3 millilitres). Cartridges are available in packs of 5 or 10. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Humalog 100 units/ml solution for injection in cartridges 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 Authorisation is held by Eli Lilly Nederland B.V.,
Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands.
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600

България Luxembourg/Luxemburg
TP "Eli Lilly Nederland" B.V. - Bulgaria Eli Lilly Benelux S.A./N.V.
tel. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84

Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100

Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500

Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800

Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00

Ελλάδα Österreich
FARMASERV-LILLY A.E.B.E. Eli Lilly Ges. m.b.H.
Tel: +30 210 629 4600 Tel: + 43-(0) 1 711 780

España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00

France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600

Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000

Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10

Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111

Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250

Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Tel: +357 22 715000 Tel: + 46-(0) 8 7378800

Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000

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

Package leaflet: information for the user

Humalog Mix25 100 units/ml injectable suspension in vial

insulin lispro
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Humalog Mix25 is and what it is used for
2. What you need to know before using Humalog Mix25
3. How to use Humalog Mix25
4. Possible side effects
5. How to store Humalog Mix25
6. Contents of the pack and other information

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

Humalog Mix25 is used in the treatment of diabetes. Humalog Mix25 is a premixed suspension. The active substance it contains is insulin lispro. 25% of the insulin lispro in Humalog Mix25 is dissolved in water and acts more rapidly than regular human insulin due to a minor modification of the insulin molecule. The remaining 75% of insulin lispro in Humalog Mix25 is in suspension with protamine sulphate, resulting in a prolonged duration of action.

Your illness, diabetes, is caused by your pancreas not producing enough insulin to control blood glucose levels. Humalog Mix25 replaces the insulin your body normally produces and is used to control blood glucose over the long term. Humalog Mix25 acts more rapidly and for a longer duration than soluble insulin. You should normally inject Humalog Mix25 within 15 minutes before a meal.

Your doctor may prescribe both Humalog Mix25 and a long-acting insulin. Each type of insulin is supplied with its own package leaflet containing information on its proper use. Do not change the type of insulin unless instructed by your doctor. Exercise great caution when changing the type of insulin.

2. What you need to know before using Humalog Mix25

DO NOT use Humalog Mix25

• If you think you are experiencing hypoglycaemia (low blood sugar level). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section 3: If you take more Humalog Mix25 than you should).
  • If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and the label of the vial to confirm the name and type of insulin provided by the pharmacist. Make sure that your Humalog Mix25 package matches the one prescribed by your doctor.
• If your blood glucose level is well controlled by your current insulin therapy, you may not notice the warning signs when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet. You must pay careful attention to meal timing, frequency, and intensity of physical exercise. You should also monitor your blood sugar levels frequently by regular testing.
• Some people who have experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist, or nurse at the diabetes care center:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
• Your insulin requirements may change if you consume alcohol.
• Also inform your doctor, pharmacist, or nurse at the diabetes care center if you are planning to travel abroad. Differences in time zones between countries may require adjustments to your insulin injection and meal schedules compared to when you are at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of cerebrovascular events who were treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).

Skin changes at the injection site
You should rotate your injection sites to prevent skin changes, such as the development of lumps under the skin. Insulin may not work as effectively if you inject into an area with lumps (see section "How to use Humalog Mix25"). If you currently inject into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or that of other antidiabetic medications.

Other medicines and Humalog Mix25
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemic agents,
• acetylsalicylic acid,
• sulfonamide antibiotics,
• octreotide,
• beta2-agonists (e.g., ritodrine, salbutamol, terbutaline),
• beta-blockers,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril), or
• angiotensin II receptor antagonists.

Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those without a prescription (see section “Warnings and precautions”).

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be impaired if you experience a hypoglycaemic reaction. Consider this possibility in any situation where you might put yourself or others at risk (e.g., driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia
• have reduced or absent warning signs of hypoglycaemia

Humalog Mix25 contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially “sodium-free”.

3. How to use Humalog Mix25

Always use Humalog Mix25 exactly as your doctor has instructed you. If you have any doubts, you must
consult your doctor.
Dosage

• Normally, you should inject Humalog Mix25 within 15 minutes before a meal. If necessary, you may administer the injection immediately after the meal. Regarding amount, timing, and frequency of administration, follow your doctor's instructions precisely: they apply specifically to you. Follow them exactly and have your condition monitored regularly at the diabetes clinic.
• If you change the type of insulin you are using (for example, from animal or human insulin to a Humalog product), you may need a different dose (higher or lower) than before. This change may occur with the first injection, or it may be adjusted gradually over several weeks or months.
• Inject Humalog Mix25 subcutaneously. Do not administer the medicine by any other route. Under no circumstances should Humalog Mix25 be administered intravenously.

Preparation of Humalog Mix25

• Before use, vials containing Humalog Mix25 must be rotated gently between the palms of the hands to resuspend the insulin until it appears uniformly cloudy or milky. Do not shake vigorously, as this may cause foam formation, which could interfere with accurate dose measurement. Vials should be frequently inspected and must not be used if floating residues or white particles adhering to the bottom or walls of the vial are observed, giving it a frosted appearance. Check this before each injection.

Injection of Humalog Mix25

• First, wash your hands.

• Before injecting, disinfect the skin according to the instructions you have received. Disinfect the rubber stopper of the vial, but do not remove it.

• Use a sterile syringe and needle to puncture the rubber stopper and withdraw the required amount of Humalog Mix25 to be injected. Your doctor or diabetes clinic will
  instruct you exactly how to do this. Under no circumstances should you share syringes or
  needles with others.

• Inject the medicine subcutaneously, as you have been taught. Do not inject it directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure you have delivered the full dose. Do not rub the injection site. Make sure the injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.

If you use more Humalog Mix25 than you should
If you use more Humalog Mix25 than prescribed or are unsure of the amount injected, your blood sugar
level may drop. Check your blood sugar level.
If your blood sugar level is low (mild hypoglycemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich, as advised by your doctor, and rest. This is often sufficient to counteract mild hypoglycemia or a minor insulin overdose. If you notice your condition worsening, with shortness of breath and pale skin, inform your doctor immediately. An injection of glucagon can treat more severe hypoglycemia. Take glucose or sugar after the glucagon injection. If there is no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information on how to use glucagon.
If you forget to use Humalog Mix25
If you take less Humalog Mix25 than you need or are unsure of the amount injected, your blood sugar
level may rise. Check your blood sugar level.
Untreated hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) can become very serious and cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see sections A and B of section 4, “Possible side effects”).
Three simple precautions to avoid episodes of hypoglycemia or hyperglycemia:

• Always keep spare syringes and a vial of Humalog Mix25 available.
• Always carry identification indicating that you are diabetic.
• Always carry sugar with you.

If you stop using Humalog Mix25
If you take less Humalog Mix25 than you need, your blood sugar level may rise. Do not change the type of insulin unless instructed by your doctor.
If you have any doubts about using this medicine, consult 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 (from ≥ 1/10,000 to <1/1,000). Symptoms include:
rash all over the body
lowering of blood pressure
difficulty breathing
rapid heartbeat
shortness of breath
sweating
If you think Humalog Mix25 is causing you this type of insulin allergy, inform your doctor immediately.
Local allergy is common (from ≥ 1/100 to <1/10). In some people, the skin at the injection site may become red, swollen, and itchy. Usually, this reaction disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is uncommon (from ≥ 1/1,000 to <1/100). If you inject insulin too often in the same spot, the fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as effectively if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
Edema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood glucose control.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

Common diabetes-related problems

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• an excessive dose of Humalog Mix25 or another insulin;
• delayed or missed meals, or changes in diet;
• excessive physical exercise or work performed immediately before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• changes in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.
Typically, the first symptoms of hypoglycaemia appear rapidly and include:
tiredness
rapid heartbeat
nervousness or restlessness
feeling unwell
headache
cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycaemia may be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. Early symptoms develop slowly over several hours or days and include:
drowsiness
loss of appetite
flushing of the skin
fruity odour on the breath
thirst
feeling or signs of illness
Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical assistance.

C. Illness
If you are unwell, especially if you feel sick or have an illness, your insulin requirements may change. Even if you are not eating normally, you still need insulin. Test your urine and blood; follow the precautions you already know about when unwell, and inform your doctor.

5. How to store Humalog Mix25

Before use, store Humalog Mix25 in the refrigerator (2°C - 8°C). Do not freeze.
During use, store the vial in the refrigerator (2°C - 8°C) or at room temperature (below 30°C) and discard after 28 days. Do not place near heat sources or direct sunlight.
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers to the last day of the month indicated.
Do not use this medicine if you notice floating particles or white particles adhering to the bottom or walls of the vial, which give it a frosted appearance. Check for these signs before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package Contents and Other Information

What Humalog Mix25 100 units/ml injectable suspension in vial contains

• The active substance is insulin lispro. Insulin lispro is produced in the laboratory using a technology called "recombinant DNA technology". It is a modified form of human insulin and is therefore different from other human or animal insulins. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas.
• The excipients are protamine sulfate, m-cresol, phenol, glycerol, disodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may have been added to adjust the pH.

Description of the appearance of Humalog Mix25 100 units/ml injectable suspension in vial and
contents of the pack
Humalog Mix25 100 units/ml injectable suspension is a sterile white suspension containing
100 units of insulin lispro per millilitre (100 units/ml) of injectable suspension. 25%
of the insulin lispro in Humalog Mix25 is dissolved in water. 75% of the insulin lispro
in Humalog Mix25 is present in suspension together with protamine sulfate. Each
vial contains 1,000 units (10 millilitres). Humalog Mix25 100 units/ml injectable suspension in
vial is available in packs of 1 vial.

Marketing Authorisation Holder and Manufacturer
Humalog Mix25 100 units/ml injectable suspension in vial is manufactured by:

• Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain.

The marketing authorisation is held by Eli Lilly Nederland B.V.,
Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands.
For further information about this medicinal product, please contact the local representative of the marketing authorisation holder.

Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600

България Luxembourg/Luxemburg
ТП "Ели Лили Недерланд" Б.В. - България Eli Lilly Benelux S.A./N.V.
тел. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84

Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100

Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500

Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800

Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00

Ελλάδα Österreich
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε. Eli Lilly Ges. m.b.H.
Τηλ: +30 210 629 4600 Tel: + 43-(0) 1 711 780

España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00

France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600

Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000

Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10

Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111

Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250

Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Τηλ: +357 22 715000 Tel: + 46-(0) 8 7378800

Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000

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

Package leaflet: Information for the user

Humalog Mix25 100 units/ml injectable suspension in cartridge

insulin lispro
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Humalog Mix25 is and what it is used for
2. What you need to know before using Humalog Mix25
3. How to use Humalog Mix25
4. Possible side effects
5. How to store Humalog Mix25
6. Contents of the pack and other information

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

Humalog Mix25 is used in the treatment of diabetes. Humalog Mix25 is a premixed suspension. The active substance it contains is insulin lispro. 25% of the insulin lispro in Humalog Mix25 is dissolved in water and acts more rapidly than regular human insulin due to a minor modification of the insulin molecule. The remaining 75% of insulin lispro in Humalog Mix25 is in suspension together with protamine sulfate, resulting in a prolonged action.

Your illness, diabetes, is caused by your pancreas not producing enough insulin to properly control blood glucose levels. Humalog Mix25 replaces the insulin your body normally produces and is used to control blood glucose over the long term. Humalog Mix25 acts more rapidly and for a longer duration than soluble insulin. You should normally inject Humalog Mix25 within 15 minutes before a meal.

Your doctor may prescribe Humalog Mix25 together with a long-acting insulin. Each type of insulin comes with its own package leaflet containing information on correct use. Do not change the type of insulin unless instructed by your doctor. Exercise great caution when changing the type of insulin.

2. What you need to know before using Humalog Mix25

DO NOT use Humalog Mix25

• If you think you are experiencing hypoglycaemia (low blood sugar level). Instructions on how to manage mild hypoglycaemia are provided later in this leaflet (see section 3: If you take more Humalog Mix25 than you should).
• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and the label on the cartridge for the name and type of insulin you receive from the pharmacist. Make sure that your Humalog Mix25 pack corresponds to the one prescribed by your doctor.
• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning signs when your blood sugar level is dropping too low. These warning signs are listed later in this leaflet. You must pay close attention to meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar levels regularly by frequent testing.
• Some people who have experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the symptoms warning of hypoglycaemia were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• Inform your doctor, pharmacist, or nurse at the diabetes centre if you answer YES to any of the following questions:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
• Your insulin requirements may change if you consume alcohol.
• Also inform your doctor, pharmacist, or nurse at the diabetes centre if you are planning to travel abroad. Differences in time zones between countries may require adjustments to the timing of your insulin injections and meals compared to your usual routine at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of cerebrovascular events who were treated with pioglitazone and insulin have developed heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).

Skin changes at the injection site
Injection sites should be rotated to prevent skin changes, such as the development of lumps under the skin. Insulin may not work as effectively if you inject into an area with lumps (see section "How to use Humalog Mix25"). If you currently inject into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

Other medicines and Humalog Mix25
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemic agents,
• acetylsalicylic acid,
• sulfonamide antibiotics,
• octreotide,
• beta2-agonists (e.g., ritodrine, salbutamol, terbutaline),
• beta-blockers,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril), or
• angiotensin II receptor antagonists.

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

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be reduced if you experience a hypoglycaemic reaction. Consider this possibility in any situation where you might put yourself or others at risk (e.g., driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia, or
• have reduced or absent warning signs of hypoglycaemia.

Humalog Mix25 contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially “sodium-free”.

3. How to use Humalog Mix25

The 3 ml cartridge must only be used with Lilly 3 ml pens. Do not use with 1.5 ml pens.
Always use Humalog Mix25 exactly as directed by your doctor. If you have any doubts, consult your doctor. To prevent possible transmission of disease, each cartridge must be used by only one patient, even if the needle on the delivery device is changed.

Dose

• Normally, you should inject Humalog Mix25 within 15 minutes before a meal. If necessary, you may also inject immediately after a meal. Follow your doctor's instructions exactly regarding amount, timing, and frequency of administration—these instructions are specific to you. Follow them precisely and have your condition monitored regularly at a diabetes care center.
• If you switch the type of insulin you are using (e.g., from animal or human insulin to a Humalog product), you may require a different dose (higher or lower) than before. This change may occur with the first injection, or it may be gradually adjusted over several weeks or months.
• Inject Humalog Mix25 subcutaneously. Do not administer this medicine by any other route. Under no circumstances should Humalog Mix25 be administered intravenously.

Preparing Humalog Mix25

• Immediately before use, rotate the cartridges containing Humalog Mix25 ten times between the palms of your hands and invert them 180° ten times to resuspend the insulin until it appears uniformly cloudy or milky. If this does not occur, repeat the procedure until the components are fully mixed. The cartridges contain a small glass bead that helps mixing. Do not shake vigorously, as this may cause foaming, which could interfere with accurate dose measurement. Examine the cartridges frequently and do not use them if floating residues or white particles adhering to the bottom or sides of the cartridge are observed, giving it a frosted appearance. Check this before each injection.

Preparing the pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• You must use Humalog Mix25 cartridges only with Lilly insulin pens. Make sure the words Humalog or Lilly cartridges are mentioned in the instruction leaflet accompanying your pen. The 3 ml cartridge can only be used with a 3 ml pen.
• Follow the instructions provided with your pen. Insert the cartridge into the pen.
• Set the dose to 1 or 2 units. Hold the pen with the attached needle pointing upward and gently tap the side of the pen to move air bubbles toward the top. With the pen still pointing upward, press the injection button until a drop of Humalog Mix25 appears at the needle tip. Small air bubbles may remain in the pen; these are not dangerous, but if they are too large, they may affect the accuracy of the dose.

Injecting Humalog Mix25

• Before injecting, disinfect the skin according to the instructions you have received. Inject the medicine subcutaneously as you have been taught. Do not inject directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure each new injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.

After injection

• Immediately after completing the injection, remove the needle from the pen using the outer needle cap. This will help keep Humalog Mix25 sterile, prevent leakage of the medicine, avoid air entering the pen, and prevent needle blockage. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen. Leave the cartridge in the pen.

Subsequent injections

• Before each subsequent injection, select 1 or 2 units and press the injection mechanism while holding the pen upward until a drop of Humalog Mix25 appears at the needle tip. You can estimate how much Humalog remains in the cartridge by observing the level on its side. The distance between each mark corresponds to approximately 20 units. If there is not enough insulin left for the next dose, replace the cartridge.

Do not mix any other insulin into the Humalog Mix25 cartridge. Once the cartridge is empty, do not reuse it.

If you use more Humalog Mix25 than you should
If you use more Humalog Mix25 than prescribed or are unsure of the amount injected, your blood sugar level may drop. Check your blood sugar level.
If your blood sugar is low (mild hypoglycemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich as advised by your doctor, and rest. This is often sufficient to counteract mild hypoglycemia or a modest insulin overdose. If you notice symptoms worsening, such as shortness of breath or pale skin, contact your doctor immediately. A glucagon injection may be needed to treat more severe hypoglycemia. Take glucose or sugar after glucagon injection. If there is no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information on how to use glucagon.

If you forget to use Humalog Mix25
If you take less Humalog Mix25 than needed or are unsure of the amount injected, your blood sugar level may rise. Check your blood sugar level.
Untreated hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see sections A and B of section 4 “Possible side effects”).

Three simple precautions to avoid episodes of hypoglycemia or hyperglycemia:

• Always keep spare syringes and a vial of Humalog Mix25, or a spare pen and cartridges, in case you lose or damage your pen or cartridges.
• Always carry identification indicating that you are diabetic.
• Always carry sugar with you.

If you stop using Humalog Mix25
If you take less Humalog Mix25 than required, your blood sugar level may increase. Do not change the type of insulin you are using unless instructed by your doctor.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody experiences them.
Systemic allergy is rare (from ≥ 1/10,000 to <1/1,000). Symptoms include:
rash over the entire body, lowering of blood pressure,
difficulty breathing, rapid heartbeat,
shortness of breath, sweating.
If you think Humalog Mix25 is causing you this type of insulin allergy, inform your doctor immediately.
Local allergy is common (from ≥ 1/100 to <1/10). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is not common (from ≥ 1/1,000 to <1/100). If you inject insulin too often in the same spot, fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin may also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as effectively if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
Edema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood glucose control.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system. By reporting side effects, you can help provide more information on the safety of this medicine.

Common diabetes-related problems

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means that there is not enough sugar in the blood. Hypoglycaemia can be caused by:

• an excessive dose of Humalog Mix25 or another insulin;
• a delayed or missed meal, or a change in diet;
• excessive physical exercise or work performed just before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• a change in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycaemia appear rapidly and include:
tiredness, rapid heartbeat,
nervousness or restlessness, feeling unwell,
headache, cold sweat.
If you are unable to recognize the warning symptoms of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means that there is not enough insulin in your body. Hyperglycaemia can be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:
drowsiness, loss of appetite,
flushed face, fruity-smelling breath,
thirst, feeling or showing signs of illness.
Heavy breathing and rapid pulse are serious symptoms. Seek immediate medical help.

C. Illness
If you are ill, especially if you feel unwell, your insulin requirements may vary. Even if you are not eating normally, you still need insulin. Test your urine and blood; when unwell, follow the precautions you already know and inform your doctor.

5. How to store Humalog Mix25

Before use, store Humalog Mix25 in the refrigerator (2°C - 8°C). Do not freeze.
During use, store the cartridge at room temperature (below 30°C) and discard it after 28 days. Do not
place the product near a heat source or direct sunlight. Do not store the pen or cartridges being used in
the refrigerator. The pen containing the cartridge must not be stored with the needle attached.
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers
to the last day of the month.
Do not use this medicine if you notice floating particles or white particles adhering to the bottom or
sides of the cartridge, which give it a frosted appearance. Check for these signs before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Pack contents and other information

What Humalog Mix25 100 units/ml injectable suspension in cartridge contains

• The active substance is insulin lispro. Insulin lispro is produced in the laboratory using a technology called "recombinant DNA". It is a modified form of human insulin and is therefore different from other human or animal insulins. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas.
• The excipients are protamine sulfate, m-cresol, phenol, glycerol, disodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may have been added to adjust the pH.

Description of the appearance of Humalog Mix25 100 units/ml injectable suspension in cartridge and
pack contents
Humalog Mix25 100 units/ml injectable suspension is a sterile white suspension and contains
100 units of insulin lispro per millilitre (100 units/ml) of injectable suspension. 25%
of the insulin lispro contained in Humalog Mix25 is dissolved in water. 75% of the insulin lispro
contained in Humalog Mix25 is in suspension together with protamine sulfate. Each cartridge
contains 300 units (3 millilitres). Cartridges are available in packs of 5 or 10.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Humalog Mix25 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 is held by Eli Lilly Nederland B.V.,
Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands.
For further information about this medicinal product, please contact the local representative of the marketing authorization holder.

Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600

България Luxembourg/Luxemburg
TP "Eli Lilly Nederland" B.V. - Bulgaria Eli Lilly Benelux S.A./N.V.
tel. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84

Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100

Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500

Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800

Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00

Ελλάδα Österreich
Pharmaserv-Lilly A.E.B.E. Eli Lilly Ges. m.b.H.
Tel: +30 210 629 4600 Tel: + 43-(0) 1 711 780

España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00

France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600

Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000

Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10

Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111

Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250

Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Tel: +357 22 715000 Tel: + 46-(0) 8 7378800

Latvija United Kingdom
Eli Lilly (Suisse) S.A. Latvia Branch Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000

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

Package leaflet: Information for the user

Humalog Mix50 100 units/ml injectable suspension in cartridge

insulin lispro
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be dangerous.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Humalog Mix50 is and what it is used for
2. What you need to know before using Humalog Mix50
3. How to use Humalog Mix50
4. Possible side effects
5. How to store 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 in the treatment of diabetes. Humalog Mix50 is a premixed suspension. The active substance it contains is insulin lispro. 50% of the insulin lispro in Humalog Mix50 is dissolved in water and acts more rapidly than regular human insulin due to a minor modification of the insulin molecule. The other 50% of insulin lispro in Humalog Mix50 is in suspension together with protamine sulfate, resulting in a prolonged action.

Your condition, diabetes, arises because your pancreas does not produce sufficient insulin to control blood glucose levels. Humalog Mix50 replaces the insulin normally produced by your body and is used to control glucose levels over the long term. Humalog Mix50 acts very rapidly and has a longer duration of action compared to soluble insulin. Normally, you should inject Humalog Mix50 within 15 minutes before a meal.

Your doctor may prescribe Humalog Mix50 together with a long-acting insulin. Each type of insulin comes with its own package leaflet containing information for correct use. Do not change the type of insulin unless instructed by your doctor. Exercise great caution when switching from one type of insulin to another.

2. What you need to know before using Humalog Mix50

DO NOT use Humalog Mix50

• If you think you are experiencing hypoglycaemia (low blood sugar level). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section 3: If you take more Humalog Mix50 than you should).
• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and cartridge label for the name and type of insulin provided by your pharmacist. Make sure that your Humalog Mix50 pack corresponds to the one prescribed by your doctor.
• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet. You must pay careful attention to meal timing, frequency and intensity of physical exercise. You should also monitor your blood sugar level regularly by frequent testing.
• Some people who have experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemic reaction were less pronounced or different. If you frequently experience hypoglycaemia, or have difficulty recognizing it, discuss this with your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist or diabetes care nurse:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
• Your insulin requirement may change if you consume alcohol.
• Also inform your doctor, pharmacist or diabetes care nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal times compared to your usual routine at home.
• Some patients with long-standing type 2 diabetes and a history of heart disease or previous cerebrovascular event who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).

Skin changes at the injection site
You should rotate your injection site to prevent skin changes, such as the development of lumps under the skin. Insulin may not work as effectively if you inject into an area with lumps (see section "How to use Humalog Mix50"). If you are currently injecting into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and adjust your insulin dose or that of other antidiabetic medicines.

Other medicines and Humalog Mix50
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemic agents,
• acetylsalicylic acid,
• sulfonamide antibiotics,
• octreotide,
• beta2-agonists (e.g. ritodrine, salbutamol, terbutaline),
• beta-blockers,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g. captopril, enalapril), and
• angiotensin II receptor antagonists.

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

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be reduced if you experience a hypoglycaemic reaction. Consider this possibility in any situation where you could endanger yourself or others (e.g. driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you have:

• frequent episodes of hypoglycaemia
• reduced or absent warning signs of hypoglycaemia

Humalog Mix50 contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. essentially “sodium-free”.

3. How to use Humalog Mix50

The 3 ml cartridge must only be used with Lilly 3 ml pens. Do not use with 1.5 ml pens.
Always use Humalog Mix50 exactly as prescribed by your doctor. If you have any doubts, consult your doctor. To prevent the possible transmission of disease, each cartridge must be used by only one patient, even if the needle attached to the delivery device is changed.

Dose

• Normally, you should inject Humalog Mix50 within 15 minutes before a meal. If necessary, you may administer the injection immediately after the meal. Follow your doctor’s instructions exactly regarding amount, timing, and frequency of administration—these instructions are specific to you. Adhere strictly to them and have your condition monitored regularly at a diabetes care center.
• If you switch from another type of insulin (e.g., from animal or human insulin to a Humalog product), you may require a different dose (higher or lower) than before. This change may occur with the first injection or may be gradually adjusted over several weeks or months.
• Inject Humalog Mix50 under the skin. Do not administer this medicine by any other route. Under no circumstances should Humalog Mix50 be administered intravenously.

Preparation of Humalog Mix50

• Immediately before use, rotate the cartridges containing Humalog Mix50 ten times between the palms of your hands and invert them 180° ten times to resuspend the insulin until it appears uniformly cloudy or milky. If this does not occur, repeat the procedure until the components are thoroughly mixed. The cartridges contain a small glass bead that helps mixing. Do not shake vigorously, as this may cause foaming, which could interfere with accurate dose measurement. Examine the cartridges frequently and do not use them if floating residues or white particles adhering to the bottom or walls of the cartridge are observed, giving it a frosted appearance. Check this before each injection.

Preparing the pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• You must use Humalog Mix50 cartridges only with Lilly insulin pens. Make sure the words Humalog or Lilly cartridges are mentioned in the leaflet accompanying your pen. The 3 ml cartridge can only be used with a 3 ml pen.
• Follow the instructions provided with your pen. Insert the cartridge into the pen.
• Set the dose to 1 or 2 units. Hold the pen with the attached needle pointing upward and gently tap the side of the pen to move air bubbles toward the top. With the pen still pointing upward, press the injection button until a drop of Humalog Mix50 appears at the needle tip. Small air bubbles may remain in the pen; these are not dangerous, but if they are too large, they may reduce the accuracy of the delivered dose.

Injecting Humalog Mix50

• Before injecting, disinfect the skin according to the instructions you have received. Inject the medicine subcutaneously 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 ensure the full dose has been delivered. Do not rub the injection site. Make sure each new injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.

After the injection

• Immediately after completing the injection, remove the needle from the pen using the needle's outer cap. This will help keep Humalog Mix50 sterile, prevent leakage of the medicine, stop air from entering the pen, and prevent needle blockage. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen. Leave the cartridge in the pen.

Subsequent injections

• Before each subsequent injection, select 1 or 2 units and press the injection mechanism while holding the pen upright until a drop of Humalog Mix50 appears from the needle. You can estimate how much Humalog remains in the cartridge by observing the level on its side. The distance between each mark corresponds to approximately 20 units. If there is not enough insulin left for the next dose, replace the cartridge.

Do not mix any other insulin into the Humalog Mix50 cartridge. Once the cartridge is empty, do not reuse it.

If you use more Humalog Mix50 than you should

If you use more Humalog Mix50 than prescribed or are unsure of the amount injected, your blood sugar level may drop. Check your blood sugar level.
If your blood sugar is low (mild hypoglycemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich, as advised by your doctor, and rest. This is often sufficient to counteract mild hypoglycemia or a minor insulin overdose. If you notice worsening symptoms, such as shortness of breath or pale skin, contact your doctor immediately. A glucagon injection may be needed to treat more severe hypoglycemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must be hospitalized. Ask your doctor for information on how to use glucagon.

If you forget to use Humalog Mix50

If you use less Humalog Mix50 than needed or are unsure of the amount injected, your blood sugar level may rise. Check your blood sugar level.
Untreated hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) can become very serious and cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see sections A and B of section 4, “Possible side effects”).

Three simple precautions to avoid episodes of hypoglycemia or hyperglycemia:

• Always keep a spare pen and cartridges in case you lose your pen or cartridges or they become damaged.
• Always carry identification indicating that you are diabetic.
• Always carry sugar with you.

If you stop using Humalog Mix50

If you use less Humalog Mix50 than required, your blood sugar level may rise. Do not change the type of insulin unless instructed by your doctor.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Systemic allergy is rare (from ≥ 1/10,000 to <1/1,000). Symptoms include:
rash all over the body
lowering of blood pressure
difficulty breathing
rapid heartbeat
shortness of breath
sweating
If you think Humalog Mix50 is causing you this type of insulin allergy, tell your doctor immediately.
Local allergy is common (from ≥ 1/100 to <1/10). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is not common (from ≥ 1/1,000 to <1/100). If you inject insulin too often in the same spot, the fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
Edema (e.g., swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or when therapy is changed to improve blood glucose control.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.
Common diabetes-related problems
A. Hypoglycemia
Hypoglycemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycemia may be caused by:

• an excessive dose of Humalog Mix50 or another insulin;
• a delayed or missed meal, or a change in diet;
• excessive physical exercise or work performed immediately before or after a meal;
• an infection or other illness (especially diarrhea or vomiting);
• a change in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycemia appear rapidly and include:
tiredness
rapid heartbeat
nervousness or restlessness
malaise
headache
cold sweat
If you are unable to recognize the warning signs of hypoglycemia, avoid situations—such as driving a vehicle—where hypoglycemia could put you or others at risk.
B. Hyperglycemia and diabetic ketoacidosis
Hyperglycemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycemia may be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycemia can lead to diabetic ketoacidosis. Early symptoms develop slowly over several hours or days. They include:
drowsiness
loss of appetite
flushed face
fruity-smelling breath
thirst
feeling or showing signs of illness
Heavy breathing and rapid pulse are serious symptoms. Seek immediate medical help.
C. Illness
If you are ill, especially if you feel unwell or are sick, your insulin requirements may change.
Even if you are not eating normally, you still need insulin. Test your urine and blood; when you are sick, follow the precautions you already know and inform your doctor.

5. How to store Humalog Mix50

Before use, store Humalog Mix50 in the refrigerator (2°C - 8°C). Do not freeze.
During use, store the cartridge at room temperature (below 30°C) and discard it after 28 days.
Do not place the product near a heat source or in direct sunlight. Do not refrigerate the pen or the cartridges in use.
The pen containing the cartridge must not be stored with the needle attached.
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers to the last day of the month indicated.
Do not use this medicine if floating particles or white particles adhering to the bottom or sides of the cartridge are present, giving it a frosted appearance. Check for this before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Humalog Mix50 100 units/ml injectable suspension in cartridge contains

• The active substance is insulin lispro. Insulin lispro is produced in the laboratory using a technology called "recombinant DNA". It is a modified form of human insulin and is therefore different from other human or animal insulins. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas.
• The excipients are protamine sulfate, m-cresol, phenol, glycerol, disodium phosphate 7H\ O, zinc oxide and water for injections. Sodium hydroxide or hydrochloric acid may have been added to adjust the pH.

Description of the appearance of Humalog Mix50 100 units/ml injectable suspension in cartridge and
contents of the pack
Humalog Mix50 100 units/ml injectable suspension is a sterile white suspension and contains
100 units of insulin lispro per millilitre (100 units/ml) of injectable suspension. 50%
of the insulin lispro contained in Humalog Mix50 is dissolved in water. The remaining 50% of insulin lispro
in Humalog Mix50 is present in suspension together with protamine sulfate. Each cartridge
contains 300 units (3 millilitres). Cartridges are available in packs of 5 or 10 cartridges.
Not all pack sizes may be marketed.
Marketing Authorisation 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 authorisation is held by Eli Lilly Nederland B.V.,
Papendorpseweg 83, 3528 BJ Utrecht, Netherlands.
For further information on this medicinal product, please contact the local representative of the marketing authorisation holder.
Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600
България Luxembourg/Luxemburg
ТП "Ели Лили Недерланд" Б.В. - България Eli Lilly Benelux S.A./N.V.
тел. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84
Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100
Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500
Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800
Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00
Ελλάδα Österreich
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.B.E. Eli Lilly Ges. m.b.H.
Τηλ: +30 210 629 4600 Tel: + 43-(0) 1 711 780
España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00
France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600
Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000
Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10
Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111
Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250
Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Τηλ: +357 22 715000 Tel: + 46-(0) 8 7378800
Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

Package leaflet: Information for the user

Humalog 100 units/ml KwikPen injectable solution in a pre-filled pen

insulin lispro
Each KwikPen delivers from 1 to 60 units in 1-unit increments.
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

Humalog KwikPen is used to treat diabetes. It acts more rapidly than regular human insulin due to a minor modification of the insulin molecule.
Your condition, diabetes, arises because your pancreas does not produce enough insulin to control blood glucose levels. Humalog replaces the insulin your body normally produces and is used to control glucose levels over the long term. The medicine acts very quickly and has a shorter duration of action compared to soluble insulin (2 to 5 hours). You should usually inject Humalog within 15 minutes before a meal.
Your doctor may prescribe both Humalog KwikPen and a long-acting insulin.
Each type of insulin comes with its own package leaflet containing information for correct use. Do not change the type of insulin unless instructed by your doctor. Exercise great care when switching from one type of insulin to another.
Humalog can be used in both adults and children.
The KwikPen is a disposable, prefilled pen device containing 3 ml (300 units, 100 units/ml) of insulin lispro. One KwikPen contains multiple doses of insulin. The KwikPen allows dose selection in increments of 1 unit. The number of units is displayed in the dose window; always check it before injection. You may administer from 1 to 60 units in a single injection. If your dose exceeds 60 units, you will need to give more than one injection.

2. What you must know before using Humalog KwikPen

Do NOT use Humalog KwikPen

• If you think you are experiencing hypoglycaemia (low blood sugar level). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section 3: If you use more Humalog than you should).
• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and the label of the pre-filled pen to confirm the name and type of insulin dispensed to you by the pharmacist. Make sure that your Humalog KwikPen package matches the one prescribed by your doctor.
• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet. You must pay close attention to meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar level frequently by testing.
• Some people who have experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less noticeable or different. If you frequently experience hypoglycaemia, or have difficulty recognizing it, discuss this with your doctor.
• Inform your doctor, pharmacist or diabetes care nurse if you answer YES to any of the following questions:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you exercising more than usual?
• Your insulin requirement may change if you consume alcohol.
• Also inform your doctor, pharmacist or diabetes care nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal times compared to your usual routine at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of cerebrovascular events who were treated with pioglitazone and insulin have reported the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema). This Pen must not be used by blind individuals or those with visual impairments without the assistance of a trained person.

Skin changes at the injection site
Injection sites should be rotated to prevent skin changes such as the formation of lumps under the skin. Insulin may not work as effectively if you inject into an area with lumps (see section "How to use Humalog KwikPen"). If you currently inject into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

Other medicines and Humalog KwikPen
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemic agents,
• acetylsalicylic acid,
• sulfonamide antibiotics,
• octreotide,
• beta2-agonists (e.g. ritodrine, salbutamol, terbutaline),
• beta-blockers,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g. captopril, enalapril), or
• angiotensin II receptor antagonists.

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

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be impaired during a hypoglycaemic reaction. Consider this possibility in any situation where you could put yourself or others at risk (e.g. driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you have:

• frequent episodes of hypoglycaemia, or
• reduced or absent warning symptoms of hypoglycaemia.

Humalog KwikPen contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially "sodium-free".

3. How to use Humalog KwikPen

Always use Humalog KwikPen exactly as your doctor has instructed. If you have any doubts, you should
consult your doctor. To prevent the possible transmission of diseases, each pen must be used by only
one patient, even if the needle is changed.
Dose

• Humalog should normally be injected within 15 minutes before a meal. If necessary, you may also administer the injection immediately after the meal. Follow your doctor's instructions exactly regarding the amount, timing, and frequency of administration—these instructions are specific to you. Follow them precisely and have your condition monitored regularly at the diabetes clinic.
• If you change the type of insulin you are using (for example, from animal or human insulin to a Humalog product), you may need a different dose (higher or lower) than before. This change may occur with the first injection, or it may be introduced gradually over several weeks or months.
• Humalog KwikPen is intended only for subcutaneous injections. Talk to your doctor if you need to inject insulin by another method.

Preparing Humalog KwikPen

• Humalog is already dissolved in water and therefore must not be mixed. However, make sure to use it only if it appears like water. The solution must be clear, colourless, and free from solid particles. Check this before each injection.

Preparing the KwikPen for use (refer to the instruction manual for use)

• First, wash your hands.
• Read the instructions on how to use your pre-filled insulin pen and follow them carefully. The following are some important points.
• Always use a new needle (needles are not included in the package).
• Prime the KwikPen each time before use. This allows you to check that insulin comes out and removes any air bubbles from the KwikPen. Small air bubbles may remain in the pen; these are not dangerous, but if they are too large, they may reduce the accuracy of the injected dose.

Injecting Humalog

• Before injecting, clean your skin as instructed. Inject the medicine subcutaneously as you have been taught. Do not inject it directly into a vein. After the injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure the injection site is at least one centimetre away from the previous one and remember to rotate injection sites as instructed. It does not matter which injection site you use—upper arms, thighs, buttocks, or abdomen—the action of Humalog will be even faster than that of soluble human insulin.
• Do not administer Humalog intravenously. Inject Humalog as taught by your doctor or nurse. Only your doctor may administer Humalog intravenously, and only under special circumstances such as surgery or if you are ill and your blood glucose levels are too high.

After the injection

• Immediately after completing the injection, remove the needle from the KwikPen using the outer needle cap. This will help keep the insulin sterile, prevent leakage of the medicine, stop air from entering the pen, and prevent needle blockage. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen.

Subsequent injections

• Each time you use a KwikPen, you must use a new needle. Before each injection, remove any air bubbles. You can check how much insulin remains in the pen by holding the KwikPen vertically with the needle pointing upwards. The markings on the cartridge will indicate approximately how many units remain.
• Do not mix other insulins into your disposable pen. Once the KwikPen is empty, do not reuse it. Dispose of it carefully. Your pharmacist or the staff at the diabetes clinic will advise you on how to do this.

Use of Humalog in microinfusion pumps

• The KwikPen is suitable only for subcutaneous injections. Do not use the pen to administer Humalog in any other way. If this is necessary, other formulations of Humalog 100 units/ml are available. Talk to your doctor if this applies to you.

If you use more Humalog than you should
If you use more Humalog than prescribed or are unsure of the dose injected, your blood sugar level may
decrease. Check your blood sugar level.
If your blood sugar level is low (mild hypoglycaemia), eat glucose tablets, sugar, or drink a sugary
beverage. Then eat some fruit, biscuits, or a sandwich, as advised by your doctor, and rest. This is often
sufficient to counteract mild hypoglycaemia or a minor overdose of insulin. If your condition worsens and
you experience shortness of breath and pale skin, inform your doctor immediately. A glucagon injection
can treat moderately severe hypoglycaemia. Take glucose or sugar after a glucagon injection. If there is
no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information on
the use of glucagon.
If you forget to use Humalog
If you take less Humalog than needed or are unsure of the dose injected, your blood sugar level may
increase. Check your blood sugar level.
Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very
serious and cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death
(see sections A and B in section 4 “Possible side effects”).
Three simple precautions to avoid episodes of hypoglycaemia or hyperglycaemia:

• Always keep spare syringes and a vial of Humalog, or a spare pen and cartridges, in case you lose your KwikPen or it becomes damaged.
• Always carry identification indicating that you are diabetic.
• Always carry sugar with you.

If you stop using Humalog
If you take less Humalog than needed, your blood sugar level may increase. Do not change the type of
insulin unless instructed by your doctor.
If you have any doubts about using this product, consult 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 (from ≥ 1/10,000 to <1/1,000). Symptoms include:
rash over the entire body
low blood pressure
difficulty breathing
rapid heartbeat
shortness of breath
sweating
If you think Humalog is causing you this type of insulin allergy, inform your doctor immediately.
Local allergy is common (from ≥ 1/100 to <1/10). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is not common (from ≥ 1/1,000 to <1/100). If you inject insulin too often in the same spot, the fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
Edema (for example, swelling of the arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood glucose control.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.
Common diabetes-related problems
A. Hypoglycemia
Hypoglycemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycemia can be caused by:

• an excessive dose of Humalog or another insulin;
• a delayed or missed meal, or a change in diet;
• excessive physical exercise or work performed shortly before or after a meal;
• an infection or other illness (especially diarrhea or vomiting);
• a change in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycemia appear rapidly and include:
tiredness
rapid heartbeat
nervousness or restlessness
nausea
headache
cold sweat
If you are unable to recognize the warning signs of hypoglycemia, avoid situations—such as driving a vehicle—where hypoglycemia could put yourself or others at risk.
B. Hyperglycemia and diabetic ketoacidosis
Hyperglycemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycemia can be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycemia can lead to diabetic ketoacidosis. Early symptoms develop slowly over several hours or days. They include:
drowsiness
loss of appetite
flushed face
fruity-smelling breath
thirst
feeling or evidence of illness
Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical assistance.
C. Illnesses
If you are ill, especially if you feel unwell or are sick, your insulin requirements may vary. Even when you are not eating normally, you still need insulin. Perform urine and blood tests; when you are ill, follow the precautions you already know and inform your doctor.

5. How to store Humalog KwikPen

Before use, store Humalog KwikPen in the refrigerator (2°C - 8°C). Do not freeze.
During use, store Humalog KwikPen at room temperature (below 30°C) and discard it after 28 days. Do not
expose the product to heat sources or direct sunlight. Do not refrigerate the KwikPen you are currently using.
The KwikPen must not be stored with the needle attached.
Keep out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers to the last day of the month.
Do not use this medicine if the solution appears coloured or contains solid particles. You should use it only if it looks like water. Check this before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Humalog 100 units/ml KwikPen injectable solution contains

• The active substance is insulin lispro. Insulin lispro is produced in the laboratory using a technology called "recombinant DNA". It is a modified form of human insulin and is therefore different from other human or animal insulins. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas.
• The excipients are m-cresol, glycerol, disodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may be added to adjust the pH.

Description of the appearance of Humalog KwikPen and contents of the pack
Humalog 100 units/ml KwikPen injectable solution is a sterile, clear, colourless aqueous solution containing 100 units of insulin lispro per millilitre (100 units/ml) of injectable solution. Each Humalog KwikPen contains 300 units (3 millilitres). Humalog KwikPen is available in packs of 5 pre-filled pens or in multiple packs containing 2 packs of 5 pre-filled pens. Not all pack sizes may be marketed. The Humalog 100 units/ml contained in the pre-filled pen is identical to the Humalog 100 units/ml contained in separate Humalog 100 units/ml cartridges. The KwikPen simply has an integrated cartridge. When the pre-filled pen is empty, do not reuse it.

Marketing Authorisation Holder and Manufacturer
Humalog 100 units/ml KwikPen injectable solution 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 Authorisation is held by Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, Netherlands.
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: +32-(0)2 548 84 84 Tel. +370 (5) 2649600

България Luxembourg/Luxemburg
TP "Eli Lilly Nederland" B.V. - Bulgaria Eli Lilly Benelux S.A./N.V.
tel. +359 2 491 41 40 Tél/Tel: +32-(0)2 548 84 84

Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: +420 234 664 111 Tel: +36 1 328 5100

Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: +356 25600 500

Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. +49-(0)6172 273 2222 Tel: +31-(0)30 60 25 800

Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: +372 6817 280 Tlf: +47 22 88 18 00

Ελλάδα Österreich
Pharmaserv-Lilly S.A. Eli Lilly Ges.m.b.H.
Tel: +30 210 629 4600 Tel: +43-(0)1 711 780

España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: +34-91 663 50 00 Tel: +48 22 440 33 00

France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0)1 55 49 34 34 Tel: +351-21-4126600

Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: +40 21 4023000

Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: +353-(0)1 661 4377 Tel: +386 (0)1 580 00 10

Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími +354 540 8000 Tel: +421 220 663 111

Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: +39-055 42571 Puh/Tel: +358-(0)9 85 45 250

Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Tel: +357 22 715000 Tel: +46-(0)8 7378800

Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: +371 67364000 Tel: +44-(0)1256 315000

INSTRUCTION MANUAL FOR USE
The text of the instruction manual for use is provided below.
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

Package leaflet: information for the user

Humalog Mix25 100 units/ml KwikPen injectable suspension in a pre-filled pen

insulin lispro
Each KwikPen delivers from 1 to 60 units in 1-unit increments.
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Humalog Mix25 KwikPen is and what it is used for
2. What you need to know before using Humalog Mix25 KwikPen
3. How to use Humalog Mix25 KwikPen
4. Possible side effects
5. How to store Humalog Mix25 KwikPen
6. Contents of the pack and other information

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

Humalog Mix25 KwikPen is used in the treatment of diabetes. It is a premixed suspension.
The active substance it contains is insulin lispro. 25% of the insulin lispro in
Humalog Mix25 KwikPen is dissolved in water and acts more rapidly than regular human insulin
due to a minor modification of the insulin molecule. The remaining 75% of insulin lispro in
Humalog Mix25 KwikPen is in suspension together with protamine sulfate, resulting in a prolonged
action.
Your illness, diabetes, occurs because your pancreas does not produce enough insulin to
adequately control blood glucose levels. Humalog Mix25 replaces the insulin your body normally
produces and is used to control glucose levels over the long term. Humalog Mix25
acts very rapidly and has a longer duration of action compared to soluble insulin. Usually, you
should inject Humalog Mix25 within 15 minutes before a meal.
Your doctor may prescribe both Humalog Mix25 KwikPen and a long-acting insulin.
Each type of insulin comes with its own package leaflet containing information for correct use.
Do not change the type of insulin unless instructed by your doctor. Exercise great caution when
switching from one type of insulin to another.
The KwikPen is a disposable, prefilled pen device containing 3 ml (300 units, 100 units/ml) of insulin
lispro. One KwikPen contains multiple insulin doses. The KwikPen allows you to select doses in
increments of 1 unit. The number of units is displayed in the dose window; always check it before
injection. You can administer from 1 to 60 units in a single injection. If the dose exceeds 60 units,
you will need to administer more than one injection.

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

DO NOT use Humalog Mix25 KwikPen

• If you think you are experiencing hypoglycemia (low blood sugar level). Instructions for managing mild hypoglycemia are provided later in this leaflet (see section 3: If you take more Humalog Mix25 than you should).
• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and the label of the pre-filled pen to confirm the name and type of insulin dispensed to you by the pharmacist. Make sure that your Humalog Mix25 KwikPen package corresponds to the one prescribed by your doctor.
• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet. You must pay close attention to meal timing, frequency, and physical activity. You should also monitor your blood sugar levels regularly by frequent testing.
• Some people who have experienced hypoglycemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycemic reaction were less pronounced or different. If you frequently experience hypoglycemia or have difficulty recognizing it, discuss this with your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist, or nurse at the diabetes care center:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
• Your insulin requirement may change if you consume alcohol.
• Also inform your doctor, pharmacist, or diabetes care nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal schedules compared to when you are at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of cerebrovascular events who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).
• This Pen must not be used by blind individuals or those with visual impairments without the assistance of a trained person.

Skin changes at the injection site
Injection sites should be rotated to prevent skin changes such as the development of lumps under the skin. Insulin may not work as effectively if injected into an area with lumps (see section "How to use Humalog Mix25 KwikPen"). If you are currently injecting into an area with lumps, consult your doctor before switching to another injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

Other medicines and Humalog Mix25 KwikPen
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycemics,
• acetylsalicylic acid,
• sulfonamide antibiotics,
• octreotide,
• beta2-agonists (e.g., ritodrine, salbutamol, terbutaline),
• beta-blockers,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril), or
• angiotensin II receptor antagonists.

Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription (see section "Warnings and precautions").

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be reduced during a hypoglycemic reaction. Consider this possibility in any situation where you might endanger yourself or others (e.g., driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you have:

• frequent episodes of hypoglycemia, or
• reduced or absent warning signs of hypoglycemia.

Humalog Mix25 KwikPen contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially "sodium-free".

3. How to use Humalog Mix25 KwikPen

Always use Humalog Mix25 KwikPen exactly as prescribed by your doctor. If you have any doubts,
you must consult your doctor. To prevent the possible transmission of diseases, each pen must
be used by only one patient, even if the needle is changed.
Dose

• Normally, you should inject Humalog Mix25 within 15 minutes before a meal. If necessary, you may administer the injection immediately after the meal. Follow your doctor's instructions exactly regarding amount, timing, and frequency of administration: these instructions apply exclusively to you. Follow them precisely and have your condition monitored regularly at the diabetes center.
• If you change the type of insulin you are using (for example, from animal or human insulin to a Humalog product), you might need a different dose (higher or lower) than before. This change could occur with the first injection, or it might be adjusted gradually over several weeks or months.
• Humalog Mix25 KwikPen is intended only for subcutaneous injection. Speak with your doctor if you need to administer insulin by another method.

Preparing Humalog Mix25 KwikPen

• Immediately before use, the KwikPen must be rotated ten times between the palms of the hands and inverted 180° ten times to resuspend its contents until the insulin appears uniformly cloudy or milky. If this does not happen, repeat the procedure until the components are fully mixed. The cartridges contain a small
  glass bead that facilitates mixing. Do not shake vigorously, as this may cause foaming, which could impair accurate dose measurement. The cartridges should be examined frequently and must not be used if floating residues or white particles adhering to the bottom or walls of the cartridge are observed, giving it a frost-like appearance. Check this before each injection.
  Preparing the KwikPen for use (refer to the instruction manual for use)

• First, wash your hands.

• Read the instructions on how to use your pre-filled insulin pen and follow them carefully. The following are some important points.

• Always use a new needle (needles are not included in the package). Prime the KwikPen each time before use. This ensures that insulin flows out and removes any air bubbles from the KwikPen. Small air bubbles may remain in the pen; they are not dangerous, but if they are too large, they may reduce the accuracy of the injected dose.

Injecting Humalog Mix25

• Before injecting, clean the skin according to the instructions you have received. Inject the medicine subcutaneously as you have been taught. Do not inject it directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure you have delivered the full dose. Do not rub the injection site. Make sure the injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.

After the injection

• Immediately after completing the injection, remove the needle from the KwikPen using the outer needle cap. This procedure helps maintain sterility of the insulin, prevents leakage of the medication, stops air from entering the pen, and prevents needle clogging. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen.

Subsequent injections

• Each time you use a KwikPen, you must use a new needle. Before each injection, remove any air bubbles. You can check how much insulin remains by holding the KwikPen vertically with the needle pointing upward. The markings on the cartridge will indicate approximately how many units are left.
• Do not mix other insulins into your disposable pen. Once the KwikPen is empty, do not reuse it. Dispose of it carefully. Your pharmacist or staff at the diabetes center will advise you how to do this.

If you use more Humalog Mix25 than you should
If you use more Humalog Mix25 than prescribed or are unsure of how much you have injected, your
blood sugar level may drop. Check your blood sugar level.
If your blood sugar level is low (mild hypoglycemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat some fruit, biscuits, or a sandwich, as advised by your doctor, and rest. This is often sufficient to counteract mild hypoglycemia or a minor insulin overdose. If you notice your condition worsening, with shortness of breath and pale skin, inform your doctor immediately. A glucagon injection can treat moderately severe hypoglycemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must be hospitalized. Ask your doctor for information on the use of glucagon.
If you forget to use Humalog Mix25
If you take less Humalog Mix25 than needed or are unsure of how much you have injected, your
blood sugar level may rise. Check your blood sugar level.
Untreated hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) can become very serious and cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see sections A and B of section 4 “Possible side effects”).
Three simple precautions to avoid episodes of hypoglycemia or hyperglycemia:

• Always keep spare syringes and a vial of Humalog Mix25, or a spare pen and cartridges, in case you lose your KwikPen or it becomes damaged.
• Always carry identification indicating that you are diabetic.
• Always carry sugar with you.

If you stop treatment with Humalog Mix25
If you take less Humalog Mix25 than needed, your blood sugar level may rise. Do not change the type of insulin unless instructed by your doctor.
If you have any doubts about using this product, consult your doctor or pharmacist.

4. Possible side effects

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

Systemic allergy is rare (from ≥ 1/10,000 to <1/1,000). Symptoms include:
rash over the whole body
low blood pressure
difficulty breathing
rapid heartbeat
shortness of breath
sweating
If you think Humalog Mix25 is causing you this type of insulin allergy, tell your doctor immediately.

Local allergy is common (from ≥ 1/100 to <1/10). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.

Lipodystrophy is uncommon (from ≥ 1/1,000 to <1/100). If you inject insulin too often in the same spot, the fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as effectively if you inject into an area with lumps. Change your injection site with each injection to prevent these skin changes.

Edema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood glucose control.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you help provide more information on the safety of this medicine.

Common diabetes-related problems

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means that there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• an excessive dose of Humalog Mix25 or another insulin;
• delayed or missed meals, or changes in diet;
• excessive physical exercise or work performed just before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• changes in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycaemia appear rapidly and include:
tiredness
rapid heartbeat
nervousness or restlessness
feeling unwell
headache
cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means that there is not enough insulin in your body. Hyperglycaemia may be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. Early symptoms develop slowly over several hours or days and include:
drowsiness
loss of appetite
flushing of the face
fruity odour on the breath
thirst
feeling or showing signs of illness

Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical help.

C. Illnesses
If you are ill, especially if you feel unwell or are sick, your insulin requirements may change. Even if you are not eating normally, you still need insulin. Check your urine and blood; when you are ill, follow the precautions you already know about and inform your doctor.

5. How to store Humalog Mix25 KwikPen

Before use, store Humalog Mix25 KwikPen in the refrigerator (2°C - 8°C). Do not freeze.
During use, store Humalog Mix25 KwikPen at room temperature (below 30°C) and discard after 28 days.
Do not place the product near a heat source or direct sunlight. Do not refrigerate the KwikPen in use.
Do not store the KwikPen with the needle attached.
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers to the last day of the month.
Do not use this medicine if floating particles or white particles adhering to the bottom or sides of the cartridge are present, giving it a frosted appearance. Check for this before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Humalog Mix25 100 units/ml KwikPen injectable suspension contains

• The active substance is insulin lispro. Insulin lispro is produced in the laboratory using a technology called "recombinant DNA". It is a modified form of human insulin and is therefore different from other human or animal insulins. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas.
• The excipients are protamine sulfate, m-cresol, phenol, glycerol, dibasic sodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may have been added to adjust the pH.

Description of the appearance of Humalog Mix25 100 units/ml KwikPen injectable suspension and
package contents
Humalog Mix25 100 units/ml KwikPen injectable suspension is a sterile white suspension and
contains 100 units of insulin lispro per millilitre (100 units/ml) of injectable suspension.
25% of the insulin lispro contained in Humalog Mix25 is dissolved in water. 75% of the insulin lispro
in Humalog Mix25 is in suspension together with protamine sulfate. Each
Humalog Mix25 KwikPen contains 300 units (3 millilitres). Humalog Mix25 KwikPen is available in
packs of 5 pre-filled pens or in a multiple pack containing 2 packs of 5 pre-filled pens.
Not all pack sizes may be marketed. The Humalog Mix25 contained in the KwikPen is the same as the Humalog Mix25 contained in separate Humalog Mix25 cartridges. The KwikPen simply has an integrated cartridge. When the KwikPen is empty, do not reuse it.
Marketing Authorisation Holder and Manufacturer
Humalog Mix25 100 units/ml KwikPen 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 Authorisation is held by Eli Lilly Nederland B.V.,
Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands.
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.
Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600
България Luxembourg/Luxemburg
ТП "Ели Лили Недерланд" Б.В. - България Eli Lilly Benelux S.A./N.V.
тел. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84
Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100
Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500
Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800
Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00
Ελλάδα Österreich
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε. Eli Lilly Ges. m.b.H.
Τηλ: +30 210 629 4600 Tel: + 43-(0) 1 711 780
España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00
France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600
Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000
Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10
Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111
Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250
Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Τηλ: +357 22 715000 Tel: + 46-(0) 8 7378800
Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000

INSTRUCTIONS FOR USE MANUAL
The text of the instructions for use manual is provided later on.
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

Package leaflet: information for the user

Humalog Mix50 100 units/ml KwikPen injectable suspension in a pre-filled pen

insulin lispro
Each KwikPen delivers from 1 to 60 units in 1-unit increments.
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

Humalog Mix50 KwikPen is used in the treatment of diabetes. It is a premixed suspension.
The active substance it contains is insulin lispro. 50% of the insulin lispro contained in
Humalog Mix50 KwikPen is dissolved in water and acts more rapidly than regular human insulin
due to a minor modification of the insulin molecule. The other 50% of insulin lispro contained in
Humalog Mix50 KwikPen is in suspension together with protamine sulfate, resulting in a prolonged duration of action.
Your condition, diabetes, is caused by your pancreas not producing enough insulin to properly control blood glucose levels. Humalog Mix50 replaces the insulin your body normally produces and is used to control blood glucose over the long term. Humalog Mix50 acts more rapidly and for a longer duration than soluble insulin. It is generally recommended that you inject Humalog Mix50 within 15 minutes before a meal.
Your doctor may prescribe both Humalog Mix50 KwikPen and a long-acting insulin. Each type of insulin comes with its own package leaflet containing information on correct use. Do not change the type of insulin unless instructed by your doctor. Exercise great caution when switching types of insulin.
The KwikPen is a disposable, prefilled pen device containing 3 ml (300 units, 100 units/ml) of insulin lispro. One KwikPen contains multiple doses of insulin. The KwikPen allows you to select doses in increments of 1 unit. The number of units is displayed in the dose window; always check it
before injecting. You can administer from 1 to 60 units in a single injection. If the dose
exceeds 60 units, you must administer more than one injection.

2. What you should know before using Humalog Mix50 KwikPen

Do NOT use Humalog Mix50 KwikPen

• If you think you are experiencing hypoglycaemia (low blood sugar). Instructions on how to manage mild hypoglycaemia are provided later in this leaflet (see section 3: If you take more Humalog Mix50 than you should).
• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and label of the pre-filled pen to confirm the name and type of insulin dispensed to you by the pharmacist. Make sure that your Humalog Mix50 KwikPen package matches the one prescribed by your doctor.
• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar is dropping too low. The warning signs are listed later in this leaflet. You must pay careful attention to your meal timing, frequency, and physical activity level. You should also monitor your blood sugar levels regularly by frequent testing.
• Some people who have experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• Inform your doctor, pharmacist, or diabetes care nurse if you answer YES to any of the following questions:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical activity than usual?
• Your insulin requirements may change if you consume alcohol.
• Also inform your doctor, pharmacist, or diabetes care nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal schedules compared to when you are at home.
• Some patients with long-standing type 2 diabetes and a history of heart disease or previous cerebrovascular events who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).
• This Pen must not be used by blind individuals or those with visual impairments without the assistance of a trained person.

Skin changes at the injection site
Injection sites should be rotated to prevent skin changes such as the formation of lumps under the skin. Insulin may not work as effectively if injected into an area with lumps (see section "How to use Humalog Mix50 KwikPen"). If you are currently injecting into an area with lumps, consult your doctor before switching to another injection site. Your doctor may advise you to monitor your blood glucose more closely and adjust your insulin dose or that of other antidiabetic medications.

Other medicines and Humalog Mix50 KwikPen
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemic agents,
• acetylsalicylic acid,
• sulfonamide antibiotics,
• octreotide,
• beta2-agonists (e.g., ritodrine, salbutamol, terbutaline),
• beta-blockers,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril), and
• angiotensin II receptor antagonists.

Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those without a prescription (see section “Warnings and precautions”).

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be reduced during a hypoglycaemic episode. Consider this possibility in any situation where you could endanger yourself or others (e.g., driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you:

• frequently experience hypoglycaemia, or
• have reduced or absent warning symptoms of hypoglycaemia.

Humalog Mix50 KwikPen contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially “sodium-free”.

3. How to use Humalog Mix50 KwikPen

Always use Humalog Mix50 KwikPen exactly as instructed by your doctor. If you have any doubts,
you must consult your doctor. To prevent the possible transmission of diseases, each pen must
be used by only one patient, even if the needle is changed.
Doe

• Normally, you should inject Humalog Mix50 within 15 minutes before a meal. If necessary, you may administer the injection immediately after the meal. Follow your doctor's instructions exactly regarding dose, timing, and frequency of administration: these instructions are intended solely for you. Adhere to them precisely and have your condition monitored regularly at the diabetes care center.
• If you change the type of insulin you are using (for example, from animal or human insulin to a Humalog product), you may need a different dose (higher or lower) than before. This change may occur with the first injection, or it may be adjusted gradually over several weeks or months.
• Humalog Mix50 KwikPen is intended only for subcutaneous injection. Speak with your doctor if you need to administer insulin by another method.

Preparing Humalog Mix50 KwikPen

• Immediately before use, the KwikPen must be rotated ten times between the palms of the hands and inverted 180° ten times to resuspend its contents until the insulin appears uniformly cloudy or milky. If this does not occur, repeat the procedure until the components are fully mixed. The cartridges contain a small
  glass bead that facilitates mixing. Do not shake vigorously, as this may cause foaming, which could compromise accurate dose measurement. The cartridges should be examined frequently and must not be used if floating residues or white particles adhering to the bottom or walls of the cartridge are observed, which give it a frosted appearance. Check this before each injection.
  Preparing the KwikPen for use (refer to the instruction manual for use)

• First, wash your hands.

• Read the instructions on how to use your pre-filled insulin pen and follow them carefully. Below are some important points.

• Always use a new needle (needles are not included in the package).

• Prime the KwikPen every time before use. This allows you to check that insulin flows out and to remove any air bubbles from the KwikPen. Small air bubbles may remain in the pen; they are not dangerous, but if they are too large, they may affect the accuracy of the injected dose.

Injecting Humalog Mix50

• Before injecting, clean the skin according to the instructions you have received. Inject the medication subcutaneously 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 ensure you have delivered the full dose. Do not rub the injection site. Make sure the injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.

After the injection

• Immediately after completing the injection, remove the needle from the KwikPen using the outer needle cap. This will help keep the insulin sterile, prevent leakage of medication, stop air from entering the pen, and prevent needle blockage. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen.

Subsequent injections

• Each time you use a KwikPen, you must use a new needle. Before each injection, remove any air bubbles. You can check how much insulin remains by holding the KwikPen upright with the needle pointing upward. The markings on the cartridge will indicate approximately how many units are left.
• Do not mix other insulins into your disposable pen. Once the KwikPen is empty, do not reuse it. Dispose of it carefully. Your pharmacist or diabetes care center staff will advise you how to do this.

If you use more Humalog Mix50 than you should
If you use more Humalog Mix50 than prescribed or are unsure of how much you have injected, your
blood sugar level may drop. Check your blood sugar level.
If your blood sugar level is low (mild hypoglycemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich, as your doctor has advised, and rest. This is often sufficient to counteract mild hypoglycemia or a minor insulin overdose. If you notice your condition worsening, with shortness of breath and pale skin, inform your doctor immediately. A glucagon injection may be used to treat more severe hypoglycemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information on the use of glucagon.
If you forget to use Humalog Mix50
If you use less Humalog Mix50 than needed or are unsure of how much you have injected, your
blood sugar level may rise. Check your blood sugar level.
Untreated hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) can become very serious and cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see sections A and B of section 4 “Possible side effects”).
Three simple precautions to avoid episodes of hypoglycemia or hyperglycemia:

• Always keep a spare pen and cartridges in case you lose your KwikPen or it becomes damaged.
• Always carry identification indicating that you are diabetic.
• Always carry sugar with you.

If you stop using Humalog Mix50
If you use less Humalog Mix50 than needed, your blood sugar level may rise. Do not change the type of insulin without medical advice.
If you have any doubts about using this product, consult 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 (from ≥ 1/10,000 to <1/1,000). Symptoms include:
rash over the whole body, lowering of blood pressure
difficulty breathing, rapid heartbeat
shortness of breath, sweating
If you think Humalog Mix50 is causing you this type of insulin allergy, inform your doctor immediately.
Local allergy is common (from ≥ 1/100 to <1/10). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is not common (from ≥ 1/1,000 to <1/100). If you inject insulin too often in the same spot, the fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as well as it should if you inject into an area with lumps. Change the injection site with each injection to prevent these skin changes.
Edema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood glucose control.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.
Common diabetes-related problems
A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• an overdose of Humalog Mix50 or another insulin;
• delayed or missed meals, or changes in diet;
• excessive exercise or physical exertion performed just before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• changes in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycaemia appear rapidly and include:
tiredness, rapid heartbeat
nervousness or restlessness, malaise
headache, cold sweat
If you are unable to recognize the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.
B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycaemia may be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:
drowsiness, loss of appetite
flushing of the face, fruity-smelling breath
thirst, feeling or showing signs of illness
Heavy breathing and rapid pulse are serious symptoms. Seek immediate medical attention.
C. Illness
If you are ill, especially if you feel unwell or are sick, your insulin requirements may change.
Even if you are not eating normally, you still need insulin. Test your urine and blood; when you are ill, follow the precautions you already know and inform your doctor.

5. How to store Humalog Mix50 KwikPen

Before use, store Humalog Mix50 KwikPen in the refrigerator (2°C - 8°C). Do not freeze.
During use, store Humalog Mix50 KwikPen at room temperature (below 30°C) and discard after 28 days.
Do not place the product near a heat source or expose it to direct sunlight. Do not refrigerate the KwikPen you are currently using. The KwikPen must not be stored with the needle attached.
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The expiry date refers to the last day of the month.
Do not use this medicine if you notice floating particles or white particles adhering to the bottom or sides of the cartridge, which give it a frosted appearance. Check for these signs before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Humalog Mix50 100 units/ml KwikPen injectable suspension contains

• The active substance is insulin lispro. Insulin lispro is produced in the laboratory using a technology called "recombinant DNA". It is a modified form of human insulin and is therefore different from other human or animal insulins. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas.
• The excipients are protamine sulfate, m-cresol, phenol, glycerol, disodium phosphate 7H₂O, zinc oxide and water for injections. Sodium hydroxide or hydrochloric acid may have been added to adjust the pH.

Description of the appearance of Humalog Mix50 100 units/ml KwikPen injectable suspension and contents of the pack
Humalog Mix50 100 units/ml KwikPen injectable suspension is a sterile white suspension and contains 100 units of insulin lispro per millilitre (100 units/ml) of injectable suspension. 50% of the insulin lispro contained in Humalog Mix50 is dissolved in water. The other 50% of insulin lispro in Humalog Mix50 is in suspension together with protamine sulfate. Each Humalog Mix50 KwikPen contains 300 units (3 millilitres). Humalog Mix50 KwikPen is available in packs of 5 pre-filled pens or in a multiple pack of 2 packs of 5 pre-filled pens. Not all pack sizes may be marketed. The Humalog Mix50 contained in the KwikPen is the same as that contained in separate Humalog Mix50 cartridges. The KwikPen simply has an integrated cartridge. When the KwikPen is empty, do not reuse it.

Marketing Authorisation Holder and Manufacturer
Humalog Mix50 100 units/ml KwikPen 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 authorisation is held by Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, Netherlands.
For further information about this medicinal product, please contact the local representative of the marketing authorisation holder.

Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600
България Luxembourg/Luxemburg
ТП "Ели Лили Недерланд" Б.В. - България Eli Lilly Benelux S.A./N.V.
тел. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84
Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100
Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500
Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800
Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00
Ελλάδα Österreich
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε. Eli Lilly Ges. m.b.H.
Τηλ: +30 210 629 4600 Tel: + 43-(0) 1 711 780
España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00
France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600
Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000
Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10
Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel:+ 421 220 663 111
Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250
Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Τηλ: +357 22 715000 Tel: + 46-(0) 8 7378800
Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000

INSTRUCTIONS FOR USE
The text of the instructions for use is provided below.
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

INSTRUCTIONS FOR USE
KwikPen pre-filled insulin pen
100 units/ml

READ THESE INSTRUCTIONS FOR USE BEFORE USING
Read the Instructions for Use before using the insulin and each time you use the KwikPen again. There may be new information. These instructions do not replace discussions with your healthcare provider regarding your medical condition or treatment.
The KwikPen ("Pen") is a disposable pre-filled pen containing 3 ml (300 units, 100 units/ml) of insulin. You can administer multiple doses using a single pen. The pen allows you to select doses in increments of 1 unit. You can administer from 1 to 60 units in a single injection. If your dose exceeds 60 units, you will need to administer more than one injection. The plunger moves only slightly with each injection, and you may not notice the movement. The plunger will reach the end of the cartridge only after all 300 units in the pen have been used.

Do not share your pen with other people, even if the needle has been changed. Do not reuse needles and do not share them with others. You could cause an infection in the person you lend it to or acquire an infection from the person who borrowed it.
This pen must not be used by blind or visually impaired individuals without the assistance of someone trained to use the pen.

Components of the KwikPen
Dose indicator

Components of the pen needle
(needles not included)
Paper tab

Outer cap Inner cap Needle
of needle of needle

How to recognize the KwikPen:

Materials needed for administration:

• KwikPen containing insulin
• Compatible needle for KwikPen (BD [Becton, Dickinson and Company] pen needles are recommended)
• Antiseptic swab
  Needles and antiseptic swab are not included.

Preparing the Pen

• Wash your hands with soap and water.
• Check the Pen to make sure you are using the correct type of insulin. This is particularly important if you use more than one type of insulin.
• Do not use the Pen after the expiry date printed on the Label. After you have started using the Pen, discard the Pen after the period of use specified in the Package Leaflet.
• Always use a new needle for each injection. This helps prevent infections and needle blockages.

Step 1:

• Remove the Pen cap.
  • Do not remove the Pen label.
• Clean the rubber closure with an antiseptic swab.

Step 2:

(Only for HUMALOG insulin suspensions with cloudy appearance)

• Gently rotate the Pen 10 times. And
• Invert the Pen 10 times.

Mixing is important to ensure you receive the
correct dose.
The insulin should appear uniformly mixed.
Step 3:

• Check the appearance of the insulin.
  • HUMALOG solution should appear clear and colourless. Do not use if it looks cloudy, coloured, or contains particles or clumps.
  • HUMALOG suspension – insulin with cloudy appearance – should appear white after mixing. Do not use if it appears clear or contains particles or clumps.

Step 4:

• Select a new needle.
• Remove the paper protector from the outer needle cap.

Step 5:

• Insert the needle with cap straight onto the end of the Pen and rotate the needle until it is firmly attached.

Step 6:

• Remove the outer needle cap. Do not discard it.
• Remove the inner needle cap and discard it.

Priming the Pen
Prime the Pen before each injection.

• Priming the Pen means removing any air that may have accumulated in the needle or cartridge during normal use and ensuring the Pen works properly.
• If you do not prime the Pen before each injection, you may inject too much or too little insulin.

Step 7:

• To prime the Pen, select 2 units by rotating the dose selector button.

Step 8:

• Hold the Pen with the needle pointing upwards. Tap the cartridge gently to bring air bubbles to the surface.

Step 9:

• Continue holding the Pen with the needle pointing upwards. Press the dose selector button until it stops and a “0” appears in the dose window. Keep the dose selector button pressed and count slowly to 5. You should see insulin at the tip of the needle.
  • If insulin does not appear, repeat the priming steps, but no more than 4 times.

• If insulin still does not appear, change the needle and repeat the priming steps. Small air bubbles are normal and will not affect the dose.

Selecting the Dose

• You can administer 1 to 60 units in a single injection.
• If the dose is greater than 60 units, you will need to administer more than one injection.
  • If you need help deciding how to divide the dose, consult your healthcare professional.
  • You must use a new needle for each new injection and repeat the priming step.

Step 10:

• Rotate the dose selector button until the number of units to be injected is aligned with the dose indicator. The dose indicator must line up with the selected dose.
  • The Pen allows you to select doses in 1-unit increments.

• The dose selector button clicks as you rotate it.
• DO NOT select the dose by counting the number of clicks, as this may result in an incorrect dose.
• The dose can be corrected by rotating the dose selector button in either direction until the correct dose is aligned with the dose indicator (e.g., 12 units shown in the dose window).
• Even numbers are printed on the

dial.

• Odd numbers after number 1 are shown as solid lines.
  • Always check the number in the dose window to ensure you have selected the correct dose (e.g., 25 units shown in the dose window).
  • The Pen will not allow you to select more units than are remaining in the Pen.
  • If you need to administer more units than are left in the Pen, you can:
• administer the remaining amount in the Pen and then use a new Pen to deliver the rest of the dose, or
• take a new Pen and administer the full dose.
  • It is normal to see a small amount of insulin remaining in the Pen that cannot be injected.

Injecting the Dose

• Inject insulin as shown to you by your healthcare professional.
• Change (rotate) the injection site with each injection.
• Do not try to change the dose while injecting.

Step 11:

• Choose the injection site. Insulin is injected under the skin (subcutaneously) in the abdominal area, buttocks, thighs, or upper arms.
• Clean the skin with an antiseptic swab and wait for the skin to dry before injecting the dose.

Step 12:

• Insert the needle into the skin.

• Press the dose selector button fully down.

• Keep holding the dose selector button pressed and count slowly to 5 before removing the needle.

Do not try to inject insulin by rotating the
dose selector button. Rotating the dose selector
button will NOT deliver your insulin dose.
Step 13:

• Remove the needle from the skin.

• A small drop of insulin remaining at the needle tip is normal. It will not affect the administered dose.
  • Check the number shown in the dose window.
• If you see “0” in the dose window, this means you have received the full selected dose.
• If you do not see “0” in the dose window, do not reselect the dose. Reinsert the needle into the skin and complete the injection.
• If you think you have not yet received the full dose you selected, do not restart or repeat the injection. Check your blood glucose level (blood sugar) as instructed by your healthcare professional.
• If you normally require 2 injections to administer your full dose, make sure to give the second dose.

The plunger moves only slightly with each injection,
and you may not notice the movement.
If you see blood after removing the needle from the skin,
apply light pressure to the injection site with gauze or an
antiseptic swab. Do not rub the area.
After Injection

Step 14:

• Carefully replace the outer needle cap onto the needle.

Step 15:

• Unscrew the needle with cap and dispose of it as described below (see section Disposal of the Pen and Needles).
• Do not store the Pen with the needle attached to prevent leakage, needle blockage, and air entering the Pen.

Step 16:

• Replace the cap on the Pen, aligning the cap clip with the dose indicator, and press straight onto the Pen.

Disposal of the Pen and Needles

• Place used needles in a closable, dedicated sharps container or a hard plastic container with a secure lid. Do not dispose of needles directly into household waste.
• Do not reuse the container once it is full of needles.
• Ask your healthcare professional about available options for proper disposal of the Pen and the container.
• Instructions for needle handling should not replace local institutional or healthcare professional guidelines.

Storage Instructions for the Pen
Unused Pens

• Store unused Pens in the refrigerator at a temperature between 2°C and 8°C.
• Do not freeze insulin. Do not use if it has been frozen.
• Unused Pens can be used until the expiry date printed on the label, provided the Pen has been stored in the refrigerator.

Pen in Use

• Store the Pen you are currently using at room temperature (below 30°C), protected from dust, food, liquids, heat, and light.
• Discard the Pen you are using after the time specified in the Package Leaflet, even if there is still insulin inside.

General Safety and Effective Use Information

• Keep the Pen and needles out of the sight and reach of children.
• Do not use the Pen if any part appears broken or damaged.
• Always carry an extra Pen in case you lose or damage yours.

Troubleshooting

• If you cannot remove the Pen cap, gently rotate it back and forth, then pull it off.
• If you have difficulty pressing the dose selector button:
  • Pressing the dose selector button more slowly may make the injection easier.
  • The needle may be blocked. Attach a new needle and prime the Pen.
  • There may be dust, food, or liquid inside the Pen. Discard the Pen and use a new one. You may need to request a new prescription from your doctor.

For further information or if you have problems with the KwikPen, contact your healthcare professional
for assistance or contact your local Eli Lilly branch.
Date of document revision:

Package leaflet: Information for the user

Humalog 200 units/ml KwikPen injection solution in a pre-filled pen

insulin lispro
Each KwikPen delivers from 1 to 60 units in 1-unit increments.
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Humalog 200 units/ml KwikPen is and what it is used for
2. What you need to know before using Humalog 200 units/ml KwikPen
3. How to use Humalog 200 units/ml KwikPen
4. Possible side effects
5. How to store Humalog 200 units/ml KwikPen
6. Contents of the pack and other information

1. What Humalog 200 units/ml KwikPen is and what it is used for

Humalog 200 units/ml KwikPen is used in the treatment of diabetes. Humalog acts more rapidly than normal human insulin because insulin lispro is a slightly modified form of human insulin. Insulin lispro is structurally similar to human insulin, which is a natural hormone produced by the pancreas.
Your condition, diabetes, arises because your pancreas does not produce sufficient insulin to control blood glucose levels. Humalog replaces the insulin normally produced by your body and is used to control glucose levels over the long term. The medicine acts very quickly and has a shorter duration of action compared to soluble insulin (from 2 to 5 hours). Normally, you should inject Humalog within 15 minutes before a meal.
Your doctor may prescribe both Humalog 200 units/ml KwikPen and a long-acting insulin. Each type of insulin comes with its own package leaflet containing information on correct use. Do not change the type of insulin unless instructed by your doctor.
Humalog 200 units/ml KwikPen is intended for use in adults with diabetes who require daily doses exceeding 20 units of rapid-acting insulin.
Humalog 200 units/ml KwikPen is a disposable pre-filled pen device containing 3 ml (600 units, 200 units/ml) of insulin lispro. One KwikPen contains multiple doses of insulin. The KwikPen allows you to select doses in increments of 1 unit. The number of units is displayed in the dose window; always check it before injecting. You may administer from 1 to 60 units in a single injection. If your dose exceeds 60 units, you will need to give more than one injection.

2. What you should know before using Humalog 200 units/ml KwikPen

DO NOT use Humalog 200 units/ml KwikPen

• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).
• If you suspect you are experiencing hypoglycaemia (low blood sugar). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section 3: If you use more Humalog than you should).

Warnings and precautions

• Always check the packaging and label of the pre-filled pen to confirm the name and type of insulin dispensed to you by the pharmacist. Ensure that the Humalog 200 units/ml KwikPen packaging matches the one prescribed by your doctor.
• Humalog 200 units/ml injection solution in the pre-filled pen (the KwikPen) must be injected ONLY using this pre-filled pen. Do not transfer the insulin lispro from Humalog 200 units/ml KwikPen into a syringe. The syringe’s graduated scale will not indicate the correct dose. Severe overdose may occur, leading to dangerously low blood sugar levels, which could be life-threatening. Do not transfer insulin from Humalog 200 units/ml KwikPen to any other insulin delivery device such as insulin infusion pumps.
• DO NOT mix Humalog 200 units/ml injection solution in the pre-filled pen (the KwikPen) with any other insulin or with any other medicine. Humalog 200 units/ml injection solution must not be diluted.
• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar is dropping too low. The warning signs are listed later in this leaflet in section 4. You must pay careful attention to your meal times, frequency and intensity of physical exercise. You should also closely monitor your blood sugar levels by frequent testing.
• Some people who experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• Inform your doctor, pharmacist, or diabetes care nurse if you answer YES to any of the following questions:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
• Also inform your doctor, pharmacist, or diabetes care nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal schedules compared to when you are at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of cerebrovascular events who were treated with pioglitazone and insulin have reported the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).
• This Pen must not be used by blind individuals or those with visual impairments without the assistance of a person trained to use the Pen.

Skin changes at the injection site
Injection sites should be rotated to prevent skin changes such as the formation of lumps under the skin. Insulin may not work as effectively if you inject into an area with lumps (see section “How to use Humalog 200 units/ml KwikPen”). If you currently inject into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may recommend closer monitoring of your blood glucose and possible adjustment of your insulin or other antidiabetic medication doses.

Other medicines and Humalog 200 units/ml KwikPen
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemics (e.g., metformin, acarbose, sulfonylureas, pioglitazone, empagliflozin, DPP-4 inhibitors such as sitagliptin or saxagliptin),
• acetylsalicylic acid,
• sulfonamide antibiotics,
• somatostatin analogues (such as octreotide, used to treat a rare condition where you produce too much growth hormone),
• “beta2-agonists” such as salbutamol or terbutaline for asthma, or ritodrine used to stop premature labour,
• “beta-blockers” for the treatment of hypertension, or
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol (a medicine affecting ovulation),
• certain angiotensin-converting enzyme (ACE) inhibitors used to treat certain heart conditions or hypertension (e.g., captopril, enalapril), and
• specific medicines for treating hypertension, diabetic kidney damage, and certain heart conditions (angiotensin II receptor blockers).

Inform your doctor if you are taking, have recently taken, or might take any other medicine (also see section “Warnings and precautions”).

Humalog and alcohol
Drinking alcohol may alter (increase or decrease) your blood sugar levels. Therefore, your insulin requirement may change.

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet.

Ask your doctor for advice.

Driving and using machines
Your ability to concentrate and react may be reduced during a hypoglycaemic episode. Consider this risk in any situation where you could endanger yourself or others (e.g., driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia
• have reduced or absent warning symptoms of hypoglycaemia

Humalog 200 units/ml KwikPen contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially “sodium-free”.

3. How to use Humalog 200 units/ml KwikPen

Always use this medicine exactly as instructed by your doctor. If you have any doubts, you must
consult your doctor. To prevent possible transmission of disease, each pen must be used by only
one patient, even if the needle is changed.
Humalog 200 units/ml KwikPen is intended for patients who require more than 20 units of rapid-acting
insulin per day.
Do not transfer insulin lispro from Humalog 200 units/ml KwikPen into a syringe. The scale
on the insulin syringe will not indicate the correct dose. A serious overdose may occur, causing a
dangerous drop in blood sugar levels, which could be life-threatening.
Do not use Humalog 200 units/ml KwikPen injectable solution in an insulin infusion pump.

Dose

• Normally, you should inject Humalog within 15 minutes before a meal. If necessary, you may inject immediately after the meal. Follow your doctor’s instructions exactly regarding amount, timing, and frequency of administration—these instructions are specific to you. Follow them precisely and have your condition monitored regularly at the diabetes care center.
• If you switch the type of insulin you are using (for example, from animal or human insulin to a Humalog product), you may need a different amount (higher or lower) than before. This change may occur with the first injection or may be adjusted gradually over several weeks or months.
• Inject Humalog under the skin (subcutaneously).

Preparation of Humalog 200 units/ml KwikPen

• Humalog is already dissolved in water and therefore must not be mixed. However, make sure to use it only if it appears like water. The solution must be clear, colorless, and free of solid particles. Check this before each injection.

Preparing the KwikPen for use (refer to the instruction manual for use)

• First, wash your hands.
• Read the instructions on how to use the prefilled insulin pen and follow them carefully. The following are some important points.
• Always use a new needle (needles are not included in the package).
• Prime the KwikPen each time before use. This allows you to check that insulin comes out and removes any air bubbles from the pen. Small air bubbles may remain in the pen; they are not dangerous, but if they are too large, they may affect the accuracy of the insulin dose.

Injecting Humalog

• Before injecting, clean the skin as instructed. Inject the medicine subcutaneously as you have been taught. After injection, leave the needle in the skin for 5 seconds to ensure you have delivered the full dose. Do not rub the injection site. Make sure the injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as you have been taught. It does not matter whether you use the upper arms, thighs, buttocks, or abdomen—the action of Humalog will be even faster than that of soluble human insulin.
• Do not inject Humalog 200 units/ml KwikPen injectable solution directly into a vein (intravenously).

After injection

• Immediately after completing the injection, remove the needle from the KwikPen using the outer needle cap. This procedure helps keep the insulin sterile, prevents leakage of the medicine, stops air from entering the pen, and helps prevent needle blockage. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen.

Subsequent injections

• Each time you use a KwikPen, you must use a new needle. Before each injection, remove any air bubbles. You can check how much insulin remains in the KwikPen by holding it upright with the needle pointing upward.
• Once the KwikPen is empty, do not reuse it. Dispose of it carefully. Your pharmacist or diabetes care center staff will advise you how to do this.

If you use more Humalog than you should
If you use more Humalog than prescribed or are unsure of the amount injected, your blood sugar level may drop.
Check your blood sugar level.
If your blood sugar level is low (mild hypoglycemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich, as advised by your doctor, and rest. This is often sufficient to counteract mild hypoglycemia or a minor insulin overdose. If you notice worsening symptoms, such as shortness of breath or pale skin, contact your doctor immediately. An injection of glucagon can treat moderately severe hypoglycemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must go to the hospital. Ask your doctor for information on how to use glucagon.

If you forget to use Humalog
If you take less Humalog than needed or are unsure of the amount injected, your blood sugar level may rise.
Check your blood sugar level.
Untreated hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) can become very serious and cause headache, feeling unwell (nausea), being sick (vomiting), fluid loss (dehydration), loss of consciousness, coma, and even death (see section 4 “Possible side effects”).

Three simple precautions to avoid episodes of hypoglycemia or hyperglycemia:

• Always carry a spare pen in case you lose your KwikPen or it becomes damaged.
• Always carry identification showing that you have diabetes.
• Always carry some sugar with you.

If you stop using Humalog
If you take less Humalog than required, your blood sugar level may increase. Do not change the type of insulin unless instructed by your doctor.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Severe allergic reaction is rare (may affect up to 1 in 1,000 people). Symptoms include:
rash over the whole body
lowering of blood pressure
difficulty breathing
rapid heartbeat
shortness of breath
sweating
If you think Humalog is causing you this type of allergic reaction to insulin, contact a doctor immediately.
Local allergic reaction is common (may affect up to 1 in 10 people). In some people, the skin around the injection site may become red, swollen and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is not common (may affect up to 1 in 100 people). If you inject insulin too often into the same spot, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as well as it should if you inject into an area with lumps. Change your injection site with each injection to prevent these skin changes.
Edema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood sugar control.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

Common diabetes-related problems

Hypoglycemia
Hypoglycemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycemia may be caused by:

• an overdose of Humalog or another insulin;
• a delayed or missed meal, or a change in diet;
• excessive physical exercise or work done immediately before or after a meal;
• an infection or other illness (especially diarrhea or vomiting);
• a change in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with blood sugar levels (see section 2).
Usually, the first symptoms of hypoglycemia appear quickly and include:
tiredness
rapid heartbeat
nervousness or restlessness
feeling unwell
headache
cold sweat
If you are unable to recognize the warning signs of hypoglycemia, avoid situations—such as driving a vehicle—where hypoglycemia could put you or others at risk.

Hyperglycemia and diabetic ketoacidosis
Hyperglycemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycemia may be caused by:

• missing a dose of Humalog or another insulin;
• taking a lower dose of insulin than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycemia may lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:
drowsiness
loss of appetite
flushed face
fruity breath odor
thirst
feeling or evidence of illness
Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical help.

Illness
If you are ill, especially if you feel or know you are unwell, your insulin requirements may change. Even when you are not eating normally, you still need insulin. Test your urine and blood; when you are ill, follow the “appropriate precautions” and inform your doctor.

5. How to store Humalog 200 units/ml KwikPen

Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton.
The expiry date refers to the last day of that month.
Before use, store Humalog 200 units/ml KwikPen in the refrigerator (2°C - 8°C). Do not freeze.
During use, store Humalog 200 units/ml KwikPen at room temperature (below 30°C)
and discard it after 28 days. Do not place the medicine near heat sources or direct sunlight.
Do not store the KwikPen you are currently using in the refrigerator. The KwikPen must not be
stored with the needle attached.
Do not use this medicine if you notice that the solution is coloured or contains solid particles. You must
use it only if it appears clear and like water. Check this before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Humalog 200 units/ml KwikPen Injectable Solution Contains

• The active substance is insulin lispro. Each ml of injectable solution contains 200 units (U) of insulin lispro. Each pre-filled pen (3 ml) contains 600 units (U) of insulin lispro.
• The excipients are metacresol, glycerol, tromethamine, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may have been added to adjust the pH.

Description of the Appearance of Humalog 200 units/ml KwikPen and Contents of the Package
Humalog 200 units/ml KwikPen injectable solution is a sterile, clear, colourless aqueous solution and contains 200 units of insulin lispro per millilitre (200 units/ml) of injectable solution. Each Humalog 200 units/ml KwikPen contains 600 units (3 millilitres). Humalog 200 units/ml KwikPen is available in packs of 1, 2 or 5 pre-filled pens or in multiple packs containing 2 packs of 5 pre-filled pens each. Not all pack sizes may be marketed. The KwikPen contains a built-in cartridge. When the pre-filled pen is empty, do not reuse it.
Marketing Authorisation Holder
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands.
Manufacturer
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.
For further information about this medicine, contact the local representative of the Marketing Authorisation Holder.
Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600
България Luxembourg/Luxemburg
TP "Eli Lilly Nederland" B.V. - Bulgaria Eli Lilly Benelux S.A./N.V.
tel. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84
Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100
Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500
Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800
Eesti Norge
Eli Lilly Nederland B.V. filiaal Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00
Ελλάδα Österreich
FARMASERV-LILLY S.A.E. Eli Lilly Ges. m.b.H.
Tel: +30 210 629 4600 Tel: + 43-(0) 1 711 780
España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00
France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600
Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000
Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10
Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111
Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250
Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Tel: +357 22 715000 Tel: + 46-(0) 8 7378800
Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000

INSTRUCTIONS FOR USE
The text of the Instructions for Use is provided below.
More detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/

INSTRUCTIONS FOR USE
Humalog 200 units/ml KwikPen Injectable Solution in a Pre-filled Pen
insulin lispro

READ THIS INSTRUCTIONS FOR USE BEFORE USING

Read the Instructions for Use before using Humalog 200 units/ml KwikPen injectable solution and each time you use Humalog 200 units/ml KwikPen again. There may be new information. These instructions do not replace discussions with your healthcare provider about your medical condition or treatment.
Humalog 200 units/ml KwikPen (“Pen”) is a disposable pre-filled pen containing 3 ml (600 units, 200 units/ml) of insulin lispro injectable solution. You can administer multiple doses using a single pen. The Pen allows you to select doses in 1-unit increments. You can deliver from 1 to 60 units in a single injection. If your dose exceeds 60 units, you must administer more than one injection. The plunger moves only slightly with each injection and you may not notice the movement. The plunger will reach the end of the cartridge only after you have used all 600 units in the Pen.
This pen has been designed to allow you to inject higher doses than other pens you may have used previously. Select your usual dose as instructed by your healthcare provider.
Humalog KwikPen is available in two concentrations: 100 units/ml and 200 units/ml. Inject Humalog 200 units/ml ONLY using the Pen. DO NOT transfer insulin from the Pen to any other insulin delivery device.
Syringes and insulin infusion pumps will not correctly deliver 200 units/ml insulin. A serious overdose may occur, causing dangerously low blood sugar levels, which could be life-threatening.
Do not share your Pen with other people, even if the needle has been changed. Do not reuse or share needles. You could transmit an infection to the person borrowing it or acquire an infection from them.
This Pen must not be used by blind or visually impaired individuals without the assistance of someone trained to use the Pen.

Components of the KwikPen

Components of the Pen Needle Dose selector button
(needles not included) with burgundy (plum) ring
Needle

Outer needle cap Inner needle cap Paper tab

How to Recognise Humalog 200 units/ml KwikPen:

• Pen colour: Dark grey
• Dose selector button: Dark grey with a burgundy (plum) ring at the end
• Labels: Burgundy (plum) colour, with “200 units/ml” in a yellow box
• Yellow warning on the cartridge holder

Items Needed for Administration:

• Humalog 200 units/ml KwikPen
• Compatible needle for KwikPen (recommended BD [Becton, Dickinson and Company] pen needles)
• Alcohol swab
• Needles and alcohol swabs are not included.

Preparing the Pen

• Wash your hands with soap and water.
• Check the Pen to ensure you are using the correct type of insulin. This is especially important if you use more than one type of insulin.
• Do not use the Pen after the expiry date printed on the label or for more than 28 days after you started using it.
• Always use a new needle for each injection. This helps prevent infections and needle blockages.

Step 1:
Remove the Pen cap.

• Do not remove the Pen label.

Clean the rubber closure with an alcohol swab.

Humalog 200 units/ml injectable solution should appear clear and colourless. Do not use if it looks cloudy, coloured, or contains particles or clumps.
Step 2:

Choose a new needle.
Remove the paper tab from the outer needle cap.
Step 3:

Attach the needle with its cap straight onto the end of the Pen and rotate the needle until it is securely fastened.
Step 4:

Remove the outer needle cap. Do not discard it.
Remove the inner needle cap and discard it.

Priming the Pen
Prime the Pen before each injection.

• Priming the Pen means removing any air that may have accumulated in the needle or cartridge during normal use and ensuring the Pen is working properly.
• If you do not prime the Pen before each injection, you may inject too much or too little insulin.

Step 5:

To prime the Pen, select 2 units by rotating the dose selector button.
Step 6:

Hold the Pen with the needle pointing upward.
Tap the cartridge gently to bring any air bubbles to the surface.
Step 7:

Keep holding the Pen with the needle pointing upward. Press the dose selector button until it stops and a “0” appears in the dose window. Keep pressing the dose selector button and count slowly to 5.

• You should see insulin at the tip of the needle.
  • If insulin does not appear, repeat the priming steps, but no more than

8 times.

• If insulin still does not appear, change the needle and repeat the priming steps. Small air bubbles are normal and will not affect dosing.

Selecting the Dose
This pen has been designed to deliver the dose shown in the dose window. Select your usual dose as instructed by your healthcare provider.

• You can administer from 1 to 60 units in a single injection.
• If your dose exceeds 60 units, you must administer more than one injection.
  • If you need help deciding how to split your dose, ask your healthcare provider.
  • You must use a new needle for each new injection and repeat the priming step.

Step 8:

Rotate the dose selector button to the number of units you need to inject. The dose indicator must align with the dose.

• The Pen allows you to select doses in 1-unit increments.
• The dose selector button clicks

as you rotate it.

• DO NOT select your dose by counting clicks, as this may result in an incorrect dose.
• You can correct the dose by rotating the dose selector button in either direction until the correct dose aligns with the dose indicator. (Example: 12 units shown in the dose window)
• Even numbers are printed on the dial. (Example: 12 units shown in the dose window)
• Odd numbers after 1 are

shown as solid lines.
Always check the number in the dose window to ensure you have selected the correct dose. (Example: 25 units shown in the dose window)

• The Pen will not allow you to select more units than are remaining in the Pen.
• If you need to administer more units than are remaining in the Pen, you can:
  • administer the remaining amount in the Pen and then use a new Pen to deliver the rest of your dose, or
  • take a new Pen and administer the full dose.

Injecting the Dose

• Inject insulin as shown to you by your healthcare provider.
• Change (rotate) the injection site for each injection.
• Do not attempt to change the dose while injecting.

Step 9:

Choose your injection site.
Humalog 200 units/ml injectable solution is injected under the skin (subcutaneously) in the abdominal area, buttocks, thighs, or upper arms.
Clean the skin with an alcohol swab and wait for the skin to dry before injecting the dose.
Step 10:
Insert the needle into the skin.

Press the dose selector button fully down.
Continue holding the

dose selector button and count slowly to 5 before removing the needle.
Do not try to inject insulin by rotating the dose selector button. Rotating the dose selector button will NOT deliver your insulin dose.
Step 11:
Remove the needle from the skin.

• A small drop of insulin remaining at the needle tip is normal and will not affect the delivered dose.

Check the number shown in the dose window.

• If you see “0” in the dose window, this means you have delivered the full selected dose.
• If you do not see “0” in the dose window, do not reselect the dose. Reinsert the needle into the skin and complete your injection.
• If you think you have not yet received the full dose you selected, do not restart or repeat the injection. Check your blood glucose level as instructed by your healthcare provider.
  The plunger moves only slightly with each injection and you may not notice the movement.
  If you see blood after removing the needle from the skin, apply gentle pressure to the injection site with gauze or an alcohol swab.
  Do not rub the area.

After Injection
Step 12:

Carefully replace the outer needle cap onto the needle.
Step 13:

Unscrew the needle with its cap and dispose of it as described below (see section Disposal of the Pen and Needles).
Do not store the Pen with the needle attached to prevent leakage, needle blockage, and air entering the Pen.
Step 14:

Replace the Pen cap by aligning the cap clip with the dose indicator and press straight onto the Pen.

Disposal of the Pen and Needles

• Place used needles in a closable, puncture-resistant sharps container or a hard plastic container with a secure lid. Do not dispose of needles directly into household waste.
• Do not reuse the container once it is full of needles.
• Ask your healthcare provider about appropriate disposal options for the Pen and the container.
• Instructions for needle handling should not replace local institutional or healthcare provider regulations.

Storage Instructions for the Pen
Unused Pens

• Store unused Pens in a refrigerator at 2°C to 8°C.
• Do not freeze Humalog 200 units/ml injectable solution. Do not use if it has been frozen.
• Unused Pens may be used until the expiry date printed on the label, provided they have been stored in the refrigerator.
  Pen in Use
• Store the Pen you are currently using at room temperature (below 30°C), protected from dust, food, liquids, heat, and light.
• Discard the Pen you are using after 28 days, even if it still contains insulin.

General Safety and Effective Use Information

• Keep the Pen and needles out of sight and reach of children.
• Do not use the Pen if any part appears broken or damaged.
• Always carry a spare Pen in case you lose or damage your current one.

Troubleshooting

• If you cannot remove the Pen cap, gently twist it back and forth, then pull it off.
• If you have difficulty pushing the dose selector button:
  • Pushing the dose selector button more slowly may make injection easier.
  • The needle may be blocked. Attach a new needle and prime the Pen.
  • There may be dust, food, or liquid inside the Pen. Discard the Pen and use a new one. You may need to request a new prescription from your doctor.
• Do not transfer insulin from the Pen to a syringe or insulin infusion pump. A serious overdose may occur.

For further information or if you have any problems with Humalog 200 units/ml KwikPen, contact your healthcare provider for assistance or contact your local Eli Lilly office.
Date of revision of the document:

Package Leaflet: Information for the User

Humalog 100 units/ml Junior KwikPen solution for injection in a pre-filled pen

insulin lispro
Each Junior KwikPen delivers from 0.5 to 30 units in 0.5 unit increments
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including any not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

Humalog Junior KwikPen is used in the treatment of diabetes. Humalog acts more rapidly than regular human insulin due to a small modification of the insulin molecule. Insulin lispro is structurally similar to human insulin, a natural hormone produced by the pancreas. Your condition, diabetes, arises because your pancreas does not produce enough insulin to control blood glucose levels. Humalog replaces the insulin normally produced by your body and is used to control glucose levels over the long term. The medicine acts very quickly and has a shorter duration of action compared to soluble insulin (from 2 to 5 hours). Humalog should usually be injected within 15 minutes before a meal.

Your doctor may prescribe both Humalog and a long-acting insulin. Each type of insulin comes with its own package leaflet containing information for correct use. Do not change the type of insulin unless instructed by your doctor.

Humalog can be used in both adults and children.

Humalog 100 units/ml Junior KwikPen is a disposable pre-filled pen device containing 3 ml (300 units, 100 units/ml) of insulin lispro. A KwikPen contains multiple insulin doses. The KwikPen allows dose selection in half-unit increments (0.5 units). The number of units is displayed in the dose window; always check it before injection. You may administer from 0.5 units to 30 units in a single injection. If the dose required exceeds 30 units, you will need to give more than one injection.

2. What you need to know before using Humalog Junior KwikPen

DO NOT use Humalog Junior KwikPen

• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).
• If you suspect that you are experiencing hypoglycaemia (low blood sugar level). Instructions on how to manage mild hypoglycaemia are provided later in this leaflet (see section 3: If you use more Humalog than you should).

Warnings and precautions

• Always check the packaging and label of the pre-filled pen to confirm the name and type of insulin dispensed by your pharmacist. Make sure that your pack of Humalog 100 units/ml Junior KwikPen matches the one prescribed by your doctor.
• DO NOT mix Humalog 100 units/ml injectable solution in the pre-filled pen (the Junior KwikPen) with any other insulin or with any other medicine.
• If your blood glucose level is well controlled by your current insulin therapy, you may not notice the warning symptoms when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet in section 4. You must pay close attention to meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar levels frequently.
• Some people who have experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less pronounced or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist, or diabetes care nurse:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you exercising more than usual?
• Also inform your doctor, pharmacist, or diabetes care nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal schedules compared to when you are at home.
• Some patients with longstanding type 2 diabetes and heart disease or a history of cerebrovascular events who were treated with pioglitazone and insulin have reported the development of heart failure. Inform your doctor as soon as possible if you develop signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (oedema).
• This Pen must not be used by blind individuals or those with visual impairments without the assistance of trained persons.

Skin changes at the injection site
Injection sites should be rotated to prevent skin changes such as the formation of lumps under the skin. Insulin may not work as effectively if injected into an area with lumps (see section "How to use Humalog Junior KwikPen"). If you are currently injecting into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or that of other antidiabetic medicines.

Other medicines and Humalog Junior KwikPen
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemics (e.g. metformin, acarbose, sulfonylurea agents, pioglitazone, empagliflozin, DPP-4 inhibitors such as sitagliptin or saxagliptin),
• acetylsalicylic acid,
• sulfonamide antibiotics,
• somatostatin analogues (such as octreotide, used to treat a rare condition in which you produce too much growth hormone),
• “beta2-agonists” such as salbutamol or terbutaline for asthma treatment, or ritodrine used to stop premature labour,
• “beta-blockers” for the treatment of hypertension,
• certain antidepressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors),
• danazol (a medicine affecting ovulation),
• certain angiotensin-converting enzyme (ACE) inhibitors used for treating certain heart conditions or hypertension (e.g. captopril, enalapril), and
• specific medicines for treating hypertension, diabetic kidney damage, and certain heart conditions (angiotensin II receptor blockers).

Inform your doctor if you are taking, have recently taken, or might take any other medicine (see section “Warnings and precautions”).

Humalog and alcohol
Drinking alcohol may alter (increase or decrease) your blood sugar level. Therefore, your insulin requirement may change.

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor.

Driving and using machines
Your ability to concentrate and react may be reduced if you experience a hypoglycaemic reaction. Consider this possibility in any situation where you might endanger yourself or others (e.g. driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia
• have reduced or absent warning signs of hypoglycaemia

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

3. How to use Humalog Junior KwikPen

Always use this medicine exactly as instructed by your doctor. If you have any doubts, you must
consult your doctor. To prevent the possible transmission of diseases, each pen must be
used by only one patient, even if the needle is changed.
Dose

• The number of half units (0.5 units) is visible in the dose display window of the pen. Half units (0.5 units) are indicated as lines between the numbers.
• Always check the number shown in the dose display window to ensure you have selected the correct dose.
• Normally, you should inject Humalog within 15 minutes before a meal. If necessary, you may also administer the injection immediately after the meal. Follow your doctor's instructions exactly regarding amount, timing, and frequency of administration; these instructions are specific to you. Follow them precisely and have regular check-ups at the diabetes clinic.
• If you switch the type of insulin you are using (for example, from animal or human insulin to a Humalog product), you may need a different amount of medicine (higher or

lower) than before. This change may occur with the first injection, or it may be gradually adjusted over a period of several weeks or months.

• Humalog KwikPen is intended only for subcutaneous injections. Speak with your doctor if you need to administer insulin by another method.

Preparing Humalog Junior KwikPen

• Humalog is already dissolved in water, so you must not mix it. However, make sure to use it only if its appearance is the same as that of water. The solution must be clear, colourless, and free of solid particles. Check this before each injection.

Preparing the Junior KwikPen for use (refer to the instruction manual for use)

• First, wash your hands.
• Read the instructions on how to use your pre-filled insulin pen and follow them carefully. The following are some important points.
• Always use a new needle (needles are not included in the package).
• Prime the Junior KwikPen every time before use. This allows you to check that insulin comes out and to remove any air bubbles from the Junior KwikPen. Small air bubbles may remain in the pen; they are not dangerous, but if they are too large, they may reduce the accuracy of the insulin dose injected.

Injecting Humalog

• Before injecting, clean the skin according to the instructions you have received. Inject the medicine subcutaneously, as you have been taught. Do not inject it directly into a vein. After the injection, leave the needle in the skin for 5 seconds to ensure you have delivered the full dose. Do not rub the injection site. Make sure the injection site is at least one centimetre away from the previous one, and remember to rotate injection sites as instructed. It does not matter which injection site you use—whether the upper arms, thighs, buttocks, or abdomen—the action of Humalog will be even faster than that of soluble human insulin.
• You must not administer Humalog intravenously. Inject Humalog as taught by your doctor or nurse. Only your doctor may administer Humalog intravenously, and only under special circumstances such as during surgery or if you are ill and your blood glucose levels are too high.

After the injection

• Immediately after completing the injection, remove the needle from the Junior KwikPen using the outer needle cap. This procedure helps keep the insulin sterile, prevents leakage of the medicine, stops air from entering the pen, and prevents needle clogging. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen.

Subsequent injections

• Each time you use the Junior KwikPen, you must use a new needle. Before each injection, remove any air bubbles. You can check how much insulin remains in the Junior KwikPen by holding it vertically with the needle pointing upwards. The markings on the cartridge will indicate approximately the remaining units.
• Once the Junior KwikPen is empty, do not reuse it. Dispose of it carefully. Your pharmacist or diabetes clinic staff will advise you how to do this.

Use of Humalog in insulin infusion pumps

• The Junior KwikPen is suitable only for subcutaneous injections. Do not use the pen to administer Humalog in any other way. If this is necessary, other formulations of Humalog 100 units/ml are available. Speak with your doctor if this applies to you.

If you use more Humalog than you should
If you use more Humalog than you should, or if you are unsure of how much you have injected, your
blood sugar level may drop. Check your blood sugar level.
If your blood sugar level is low (mild hypoglycaemia), eat glucose tablets, sugar, or drink a sugary beverage.
Then eat fruit, biscuits, or a sandwich as advised by your doctor and rest. This is often sufficient to counteract mild hypoglycaemia or a minor overdose of insulin. If you notice your condition worsening, with shortness of breath and pale skin, contact your doctor immediately. An injection of glucagon can treat more severe hypoglycaemia. Take glucose or sugar after the glucagon injection. If you do not respond to glucagon, you must be admitted to hospital. Ask your doctor for information on the use of glucagon.
If you forget to use Humalog
If you take less Humalog than you need, or if you are unsure of how much you have injected, your
blood sugar level may rise. Check your blood sugar level.
Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see section 4 “Possible side effects”).
Three simple precautions to avoid episodes of hypoglycaemia or hyperglycaemia:

• Always carry a spare pen, in case you lose your Junior KwikPen or it becomes damaged.
• Always carry identification showing that you have diabetes.
• Always carry some sugar with you.

If you stop using Humalog
If you take less Humalog than you need, your blood sugar level may rise. Do not change the type of insulin unless instructed by your doctor.
If you have any doubts about using this product, consult your doctor or pharmacist.

4. Possible side effects

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

Severe allergy is rare (may affect up to 1 in 1,000 people). Symptoms include:

• Rash over the entire body
• Lowered blood pressure
• Difficulty breathing
• Rapid heartbeat
• Shortness of breath
• Sweating

If you think Humalog is causing you this type of insulin allergy, contact a doctor immediately.

Local allergy is common (may affect up to 1 in 10 people). In some people, the skin around the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.

Lipodystrophy is not common (may affect up to 1 in 100 people). If you inject insulin too often in the same spot, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as effectively if you inject into an area with lumps. Change your injection site with each injection to prevent these skin changes.

Edema (e.g., swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood sugar control.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

Common diabetes-related problems

Hypoglycaemia
Hypoglycaemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• An excessive dose of Humalog or another insulin;
• Delayed or missed meals, or changes in diet;
• Excessive physical exercise or work performed just before or after a meal;
• An infection or other illness (especially diarrhoea or vomiting);
• Changes in insulin requirements;
• Worsening of pre-existing kidney or liver disorders.

Alcohol and certain medicines can interfere with your blood sugar level (see section 2).

Usually, the first symptoms of hypoglycaemia appear quickly and include:

• Tiredness
• Rapid heartbeat
• Nervousness or restlessness
• Malaise
• Headache
• Cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.

Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycaemia may be caused by:

• Missing a dose of Humalog or another insulin;
• Taking less insulin than prescribed by your doctor;
• Eating much more food than allowed by your diet; or
• Fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days and include:

• Drowsiness
• Loss of appetite
• Flushed face
• Fruity-smelling breath
• Thirst
• Feeling or evidence of malaise

Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical assistance.

Illness
If you are ill, especially if you feel unwell or are sick, your insulin requirements may change. Even when you are not eating normally, you still need insulin. Test your urine and blood; when you are sick, follow the precautions you already know and inform your doctor.

5. How to store Humalog Junior KwikPen

Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging.
The expiry date refers to the last day of the month.
Before first use, store Humalog Junior KwikPen in a refrigerator (2°C - 8°C). Do not freeze.
During use, store Humalog Junior KwikPen at room temperature (below 30°C) and
discard after 28 days even if some solution remains. Do not place the product near
a heat source or direct sunlight. Do not store the Junior KwikPen you are currently using in the refrigerator.
The Junior KwikPen must not be stored with the needle attached.
Do not use this medicine if you notice that the solution is coloured or contains solid particles. You must
use it only if its appearance is the same as that of water. Check this before each
injection.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Humalog 100 units/ml Junior KwikPen injectable solution contains

• The active substance is insulin lispro. Each ml of solution contains 100 units (U) of insulin lispro. Each pre-filled pen (3 ml) contains 300 units (U) of insulin lispro.
• The excipients are metacresol, glycerol, disodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may be added to adjust the pH.

Description of the appearance of Humalog 100 units/ml Junior KwikPen and contents of the pack
Humalog 100 units/ml Junior KwikPen injectable solution is a sterile, clear, colourless aqueous solution containing 100 units of insulin lispro per millilitre (100 units/ml) of injectable solution. Each Humalog Junior KwikPen contains 300 units (3 millilitres). Humalog Junior KwikPen is available in packs of 1 or 5 pre-filled pens or in a multiple pack containing 2 packs of 5 pre-filled pens. Not all pack sizes may be marketed. The Junior KwikPen consists simply of an integrated cartridge. When the pre-filled pen is empty, you cannot reuse it. The Junior KwikPen is blue in colour. The dose selection button is blue with raised markings. The label is white with an orange stripe and features a burgundy (plum), yellow, and orange band. Each Junior KwikPen delivers doses from 0.5 to 30 units in increments of 0.5 units at a time.

Marketing Authorisation Holder
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, the Netherlands.

Manufacturer
Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France.

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600

България Luxembourg/Luxemburg
ТП "Ели Лили Недерланд" Б.В. - България Eli Lilly Benelux S.A./N.V.
тел. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84

Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100

Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500

Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800

Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00

Ελλάδα Österreich
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε. Eli Lilly Ges. m.b.H.
Τηλ: +30 210 629 4600 Tel: + 43-(0) 1 711 780

España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00

France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600

Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000

Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10

Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111

Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250

Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Τηλ: +357 22 715000 Tel: + 46-(0) 8 7378800

Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000

INSTRUCTION MANUAL FOR USE
The text of the instruction manual for use is provided later on.
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/ .

Instructions for use

Humalog 100 units/ml Junior KwikPen solution for injection in a pre-filled pen

insulin lispro

READ THESE INSTRUCTIONS BEFORE USE
Read the instructions for use before using Humalog Junior KwikPen and each time you need to use Humalog Junior KwikPen again. There may be new information. These instructions do not replace discussions with your healthcare provider regarding your medical condition or treatment.

Humalog 100 units/ml Junior KwikPen ("Pen") is a disposable pre-filled pen containing 3 ml (300 units, 100 units/ml) of insulin lispro solution for injection. One Pen contains multiple doses of insulin.

• Your healthcare provider will tell you how many units of insulin to administer and how to inject your prescribed dose of insulin.
• The Pen allows you to select half a unit (0.5 unit) at a time. You can administer from 0.5 unit to 30 units in a single injection.
• Always check the number shown in the dose window to ensure you have selected the correct dose.
• If your dose exceeds 30 units, you will need to administer more than one injection.
• The plunger moves only slightly with each injection and you may not notice the movement. When the plunger reaches the end of the cartridge, this means you have used all 300 units contained in the Pen.

Do not share your Pen with other people, even if the needle has been changed. Do not reuse needles and do not share them with other people. You could cause an infection in the person you lend it to or acquire an infection from the person who borrowed it.
This Pen must not be used by blind people or those with visual impairments without the assistance of a trained person.

Components of the Humalog Junior KwikPen
Dose indicator

Components of the Pen needle Dose selector button
(needles not included)
Blue, with raised markings
on the bottom and side

Paper
protector

Outer cap Needle cap Inner cap
of needle of needle

How to recognize the Humalog Junior KwikPen :

• Pen color: Blue
• Dose selector button color: Blue, with raised markings on the bottom and side
• Label: White with an orange stripe and a burgundy (plum), yellow, and orange band.

Materials needed for administration:

• Humalog Junior KwikPen
• Compatible KwikPen needle (BD [Becton, Dickinson and Company] pen needles are recommended)
• Antiseptic wipe
  Needles and antiseptic wipes are not included.

Preparing the Pen

• Wash your hands with soap and water.
• Check the Pen to make sure you are using the correct type of insulin. This is particularly important if you use more than one type of insulin.
• Do not use the Pen after the expiration date printed on the label or for more than 28 days after you started using the Pen.
• Always use a new needle for each injection. This helps prevent infections and needle blockages.

Step 1:

• Remove the Pen cap.
  • Do not remove the Pen label.
• Clean the rubber stopper with an antiseptic wipe.

Humalog should appear clear and colorless. Do not use
if it looks cloudy, colored, or contains particles or clumps.

Step 2:

• Select a new needle.
• Remove the paper protector from the outer needle cap.

Step 3:

• Attach the needle with the cap straight onto the end of the Pen and rotate the needle until it is securely fixed.

Step 4:

• Remove the outer needle cap.

Do not throw it away.

• Remove the inner needle cap and discard it.

Priming the Pen
Prime the Pen before each injection.

• Priming the Pen means removing air that may have collected in the needle or cartridge during normal use. It is important to prime the Pen so it functions properly.
• If you do not prime the Pen before each injection, you may inject too much or too little insulin.

Step 5:

• To prime the Pen, select 2 units by rotating the dose selector button.

Step 6:

• Hold the Pen with the needle pointing upward. Gently tap the cartridge to bring air bubbles to the surface.

Step 7:

• Continue holding the Pen with the needle pointing upward. Press the dose selector button until it stops and a “0” appears in the dose window. Keep pressing the dose selector button and count slowly to 5.

You should see insulin at the tip
of the needle.

• If insulin does not appear, repeat the priming steps, but no more than

4 times.

• If insulin still does not appear, change the needle and repeat the priming steps. Small air bubbles are normal and do not interfere with dosing.

Selecting the dose

• You can administer from half a unit (0.5 unit) to 30 units in a single injection. Always check the number shown in the dose window to ensure you have selected the correct dose.
• If your dose is greater than 30 units, you will need to administer more than one injection.
  • Ask your healthcare provider how to inject your dose.
  • Use a new needle for each new injection and repeat the priming step.
  • If your usual insulin requirement is typically greater than 30 units, ask your healthcare provider whether another Humalog KwikPen might be more suitable for you.

Step 8:

• Rotate the dose selector button to the number of units to be injected. The dose indicator must align with the selected dose.
  • The Pen allows selection of half units (0.5 unit) at a time.
• The dose selector button clicks as you rotate it.
• DO NOT select the dose by counting the number of clicks, as you may select an incorrect dose. Example: 4 units
• The dose can be adjusted by rotating the dose selector button in either direction until the correct dose aligns with the dose indicator.

• Numbers corresponding to whole units are printed on the dial.
• Half units are shown as lines between the numbers.

Example: 10 and a half units (10.5) shown
in the dose window

• Always check the number in the dose window to ensure you have selected the correct dose.
• The Pen will not allow you to select more units than are remaining in the Pen.
• If you need to administer more units than are left in the Pen, you can:
  • administer the remaining amount in the Pen and then use a new Pen to deliver the rest of the dose, or
  • take a new Pen and administer the full dose.
• It is normal to see a small amount of insulin remaining in the Pen that cannot be injected.

Injecting the dose

• Inject insulin as shown to you by your healthcare provider.
• Rotate (change) the injection site with each injection.
• Do not attempt to change the dose while injecting.

Step 9:

• Choose the injection site. Humalog is injected under the skin (subcutaneously) in the abdominal area, buttocks, thighs, or upper arms.
• Clean the skin with an antiseptic wipe and wait for the skin to dry before injecting the dose.

Step 10:

• Insert the needle into the skin.

• Press the dose selector button fully.

• Continue holding the dose selector button down and count slowly to 5 before removing the needle.

Do not try to inject insulin
by rotating the dose selector button.
Rotating the dose selector button
WILL NOT deliver your insulin dose.

Step 11:

• Remove the needle from the skin.
  • A small drop of insulin remaining on the needle tip is normal. It will not affect the dose administered.
• Check the number shown in the dose window.
  • If you see “0” in the dose window, this means you have administered the full selected dose.
  • If you do not see “0” in the dose window, this means you have not received the full dose. Do not reselect the dose. Reinsert the needle into the skin and complete the injection.
  • If you think you have not yet received the full dose you selected, do not restart or repeat the injection. Check your blood glucose level and contact your healthcare provider for further instructions. The plunger moves slightly with each injection and you may not notice the movement. If you see blood after removing the needle from the skin, apply light pressure to the injection site with a gauze or antiseptic wipe. Do not rub the area.

After injection

Step 12:

• Carefully replace the outer needle cap onto the needle.

Step 13:

• Unscrew the capped needle and dispose of it as described below (see section Disposal of the Pen and needles).
• Do not store the Pen with the needle attached to prevent leakage, needle blockage, and air entering the Pen.

Step 14:

• Replace the Pen cap straight onto the Pen, aligning the cap clip with the dose indicator, and press straight onto the Pen.

Disposal of the Pen and needles

• Place used needles in a closable, dedicated sharps container or a hard plastic container with a secure lid. Do not throw needles directly into household waste.
• Do not reuse the container once it is full of needles.
• Ask your healthcare provider about available options for proper disposal of the Pen and the container.
• The instructions regarding needle handling must not replace local institutional or healthcare provider regulations.

Storage instructions for the Pen
Unused Pens

• Store unused Pens in the refrigerator at a temperature between 2°C and 8°C.
• Do not freeze Humalog. Do not use if it has been frozen.
• Unused Pens can be used until the expiration date printed on the label, provided the Pen has been stored in the refrigerator.

Pen in use

• Store the Pen you are currently using at room temperature (below 30°C), protected from dust, food, liquids, heat, and light.
• Discard the Pen you are using after 28 days, even if it still contains insulin.

General safety and effective use information

• Keep the Pen and needles out of sight and reach of children.
• Do not use the Pen if any part appears broken or damaged.
• Always carry a spare Pen in case you lose or damage your current one.

Troubleshooting

• If you cannot remove the Pen cap, gently rotate it back and forth, then pull it off.
• If you have difficulty pressing the dose selector button:
  • Pressing the dose selector button more slowly may make injection easier.
  • The needle may be blocked. Attach a new needle and prime the Pen.
  • There may be dust, food, or liquid inside the Pen. Discard the Pen and use a new one. You may need to request a prescription from your doctor.

For further information or if you have any problems with Humalog 100 units/ml Junior KwikPen, contact your healthcare provider for assistance or contact your local Eli Lilly branch.
Date of document revision:

Package leaflet: information for the user

Humalog 100 units/ml Tempo Pen injectable solution in a pre-filled pen

insulin lispro
Each pre-filled pen delivers from 1 to 60 units in increments of 1 unit at a time.
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Humalog Tempo Pen is and what it is used for

Humalog Tempo Pen is used in the treatment of diabetes. Humalog acts more rapidly than normal human insulin due to a minor modification of the insulin molecule. Insulin lispro is structurally similar to human insulin, which is a natural hormone produced by the pancreas. Your condition, diabetes, arises because your pancreas does not produce sufficient insulin to control blood glucose levels. Humalog replaces the insulin normally produced by your body and is used to control glucose levels over the long term. The medicine acts very rapidly and has a shorter duration of action compared to soluble insulin (from 2 to 5 hours). Humalog should normally be injected within 15 minutes before a meal.

Your doctor may prescribe both Humalog Tempo Pen and a long-acting insulin. Each type of insulin comes with its own package leaflet containing information for correct use. Do not change the type of insulin unless directed by your doctor.

Humalog can be used in both adults and children.

The Tempo Pen is a disposable, prefilled pen device containing 3 ml (300 units, 100 units/ml) of insulin lispro. One Tempo Pen contains multiple doses of insulin. The Tempo Pen allows you to select doses in increments of 1 unit. The number of units is displayed in the dose window, always check it before injection. You can administer from 1 to 60 units in a single injection. If your dose exceeds 60 units, you will need to give more than one injection.

2. What you need to know before using Humalog Tempo Pen

DO NOT use Humalog Tempo Pen

• If you think you are experiencing hypoglycaemia (low blood sugar level). Instructions on how to manage mild hypoglycaemia are provided later in this leaflet (see section 3: If you use more Humalog than you should).
• If you are allergic to insulin lispro or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions

• Always check the packaging and label of the pre-filled pen to confirm the name and type of insulin dispensed by the pharmacist. Make sure that your pack of Humalog 100 units/ml Tempo Pen corresponds to the one prescribed by your doctor.
• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet in section 4. You must pay careful attention to meal timing, frequency and intensity of physical exercise. You should also monitor your blood sugar levels frequently.
• Some people who experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemic reaction were less obvious or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• Inform your doctor, pharmacist or diabetes nurse if you answer YES to any of the following questions:
  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
• Your insulin requirement may also change if you consume alcohol.
• Also inform your doctor, pharmacist or diabetes nurse if you are planning to travel abroad. Differences in time zones between countries may require adjustments to your insulin injection and meal times compared to your usual routine at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of cerebrovascular events who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain or localized swelling (oedema).
• This Pen must not be used by blind individuals or those with visual impairments without the assistance of trained persons.
• The Tempo Pen contains a magnet. If you have an implanted medical device, such as a cardiac pacemaker, it may not function properly if the Tempo Pen is held too close. The magnetic field extends approximately 1.5 cm.

Skin changes at the injection site
Injection sites should be rotated to prevent skin changes such as the formation of lumps under the skin. Insulin may not work as effectively if injected into an area with lumps (see section "How to use Humalog Tempo Pen"). If you currently inject into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

Other medicines and Humalog Tempo Pen
Your insulin requirements may change if you are taking:

• oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemics,
• acetylsalicylic acid,
• sulfonamide antibiotics,
• octreotide,
• "beta-2 agonists" (e.g. ritodrine, salbutamol or terbutaline),
• beta-blockers, or
• certain antidepressants (monoamine oxidase inhibitors or selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g. captopril, enalapril), or
• angiotensin II receptor blockers.

Inform your doctor if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines (see section "Warnings and precautions").

Humalog and alcohol
Alcohol consumption may increase or decrease your blood sugar level. Therefore, your insulin requirement may change.

Pregnancy and breastfeeding
Are you pregnant, planning a pregnancy, or breastfeeding? Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. Consult your doctor.

Driving and using machines
Your ability to concentrate and react may be reduced during a hypoglycaemic reaction. Consider this possibility in any situation where you could endanger yourself or others (e.g. driving a vehicle or operating machinery). You should consult your doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia
• have reduced or absent warning signs of hypoglycaemia

Humalog Tempo Pen contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially "sodium-free".

3. How to use Humalog Tempo Pen

Always use this medicine exactly as your doctor has instructed. If you have any doubts, you should
consult your doctor. To prevent the possible transmission of diseases, each pen must be used only by you,
even if the needle is changed.
Dose

• Always check the number shown in the dose display window to make sure you have selected the correct dose.
• Normally, you should inject Humalog within 15 minutes before a meal. If necessary, you may also inject immediately after the meal. Follow your doctor's instructions exactly regarding amount, timing, and frequency of administration. These instructions apply exclusively to you. Follow them precisely and have your condition monitored regularly at the diabetes clinic.
• If you change the type of insulin you are using (for example, from animal or human insulin to a Humalog product), you may need a different amount of medicine (more or less) than before. This change may occur with the first injection, or it may be gradually adjusted over several weeks or months.
• Humalog Tempo Pen is intended only for subcutaneous injections. Talk to your doctor if you need to administer insulin by another method.

Preparation of Humalog Tempo Pen

• Humalog is already dissolved in water, so you do not need to mix it. However, make sure to use it only if its appearance is the same as water. The solution must be clear, colourless, and free from solid particles. Check this before each injection.

Preparing the Tempo Pen for use (refer to the instruction manual for use)

• First, wash your hands.
• Read the instructions on how to use your pre-filled insulin pen and follow them carefully. The following are some important points.
• Always use a new needle (needles are not included in the package).
• Prime the Tempo Pen every time before use. This ensures that insulin comes out and removes any air bubbles from the Tempo Pen. Small air bubbles may remain in the pen; they are not dangerous, but if they are too large, they may affect the accuracy of the insulin dose.

Injection of Humalog

• Before injecting, clean the skin according to the instructions you have received. Inject the medicine subcutaneously as you have been taught. Do not inject it directly into a vein. After the injection, leave the needle in the skin for five seconds to ensure you have received the full dose. Do not rub the injection site. Make sure the injection site is at least one centimetre away from the previous site and remember to rotate injection sites as instructed. It does not matter whether you use the upper arm, thigh, buttocks, or abdomen—the action of Humalog will be even faster than that of soluble human insulin.
• You must not administer Humalog intravenously. Inject Humalog as taught by your doctor or nurse. Only your doctor may administer Humalog intravenously, and only under special circumstances such as surgery or if you are ill and your blood glucose levels are too high.

After the injection

• Immediately after completing the injection, remove the needle from the Tempo Pen using the outer needle cap. This will help keep the insulin sterile and prevent leakage of the medicine. It also prevents air from entering the pen and helps avoid needle blockage. Do not share your needles with others. Do not share your pen with others. Replace the cap on the pen.

If you are unsure how much insulin you have injected, check your blood sugar levels before
deciding whether you need another injection.
Subsequent injections

• Each time you use the Tempo Pen, you must use a new needle. Before each injection, remove any air bubbles. You can check how much insulin remains in the Tempo Pen by holding it vertically with the needle pointing upwards. The markings on the cartridge will indicate approximately how many units remain. DO NOT mix Humalog 100 units/ml injectable solution in the pre-filled pen with any other insulin or any other medicine.
• Once the Tempo Pen is empty, do not reuse it. Dispose of it carefully. Your pharmacist or staff at the diabetes clinic will advise you on how to do this.

Tempo Smart Button
The Tempo Pen is designed to work with the Tempo Smart Button. The optional additional component, the Tempo Smart Button, is a product available for the Tempo Pen that can be used to transmit dose information to a mobile application. The Tempo Pen can be used with or without the connected Tempo Smart Button. For further information, see the instructions provided with the Tempo Smart Button and the mobile application.
Use of Humalog in insulin pumps

• The Tempo Pen is suitable only for subcutaneous injections. Do not use the pen to administer Humalog in any other way. If this is necessary, other formulations of Humalog 100 units/ml are available. Talk to your doctor if this applies to you.

If you use more Humalog than you should
If you use more Humalog than you should, or if you are unsure how much you have injected, your blood sugar level may drop. Check your blood sugar level.
If your blood sugar level is low (mild hypoglycaemia), eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich as your doctor has advised, and rest. This is often sufficient to counteract mild hypoglycaemia or a minor overdose of insulin. If you notice that your condition worsens, with shortness of breath and pale skin, contact your doctor immediately. A glucagon injection can treat moderately severe hypoglycaemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information on the use of glucagon.
If you forget to use Humalog
If you take less Humalog than you need, or if you are unsure how much you have injected, your blood sugar level may rise. Check your blood sugar level.
Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and cause headache, feeling unwell (nausea), being sick (vomiting), fluid loss (dehydration), loss of consciousness, coma, and even death (see section 4 “Possible side effects”).
Three simple precautions to avoid episodes of hypoglycaemia or hyperglycaemia:

• Always carry a spare pen in case you lose your Tempo Pen or it becomes damaged.
• Always carry identification showing that you have diabetes.
• Always carry sugar with you.

If you stop using Humalog
If you use less Humalog than you need, your blood sugar level may rise. Do not change the type of insulin you are using unless instructed by your doctor.
If you have any questions about the use of this product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Severe allergic reaction is rare (may affect up to 1 in 1,000 people). Symptoms include:
rash over the whole body - low blood pressure
difficulty breathing - rapid heartbeat
shortness of breath - sweating
If you think Humalog is causing you this type of insulin allergy, contact a doctor immediately.
Local allergic reaction is common (may affect up to 1 in 10 people). In some people, the skin around the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.
Lipodystrophy is not common (may affect up to 1 in 100 people). If you inject insulin too often in the same spot, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as well as it should if you inject into an area with lumps. Change your injection site with each injection to prevent these skin changes.
Edema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood sugar control.
Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system detailed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.
Common diabetes problems
A. Hypoglycemia
Hypoglycemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycemia may be caused by:

• taking too much Humalog or another insulin;
• delaying or missing a meal, or changing your diet;
• excessive physical activity or exertion shortly before or after a meal;
• an infection or other illness (especially diarrhea or vomiting);
• changes in insulin requirements; or
• worsening of pre-existing kidney or liver disease.
  Alcohol and certain medicines can interfere with your blood sugar level (see section 2).
  Usually, the first symptoms of hypoglycemia appear rapidly and include:
  tiredness - rapid heartbeat
  nervousness or restlessness - feeling unwell
  headache - cold sweat
  If you are unable to recognize the warning signs of hypoglycemia, avoid situations such as driving a vehicle, in which hypoglycemia could put you or others at risk.
  B. Hyperglycemia and diabetic ketoacidosis
  Hyperglycemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycemia may be caused by:
• missing a dose of Humalog or another insulin;
• taking a lower dose of insulin than prescribed by your doctor;
• eating much more food than allowed by your diet; or
• fever, infection, or severe emotional stress.
  Hyperglycemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:
  drowsiness - loss of appetite
  flushed face - fruity-smelling breath
  thirst - feeling or signs of illness
  Heavy breathing and rapid pulse are serious symptoms. Seek immediate medical help.
  C. Illnesses
  If you are ill, especially if you feel unwell or are sick, your insulin requirements may change. Even if you are not eating normally, you still need insulin. Check your urine and blood; when you are ill, follow the precautions you already know and inform your doctor.

5. How to store Humalog Tempo Pen

Before first use, store Humalog Tempo Pen in the refrigerator (2°C - 8°C). Do not freeze.
During use, store Humalog Tempo Pen at room temperature (below 30°C) and
discard it after 28 days, even if some solution remains. Do not keep the product near a
heat source or in direct sunlight. Do not refrigerate the Tempo Pen you are currently using. The
Tempo Pen must not be stored with the needle attached.
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and packaging. The
expiry date refers to the last day of the month.
Do not use this medicine if you notice that the solution is coloured or contains solid particles. You should
use it only if it appears clear and like water. Check this before each
injection.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Humalog 100 units/ml Tempo Pen injectable solution contains

• The active substance is insulin lispro. Each ml of solution contains 100 units (U) of insulin lispro. Each pre-filled pen (3 ml) contains 300 units (U) of insulin lispro.
• The excipients are metacresol, glycerol, dibasic sodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may be added to adjust the pH.

Description of the appearance of Humalog Tempo Pen and contents of the pack
Humalog 100 units/ml Tempo Pen injectable solution is a sterile, clear, colourless aqueous solution and contains 100 units of insulin lispro per millilitre (100 units/ml) of injectable solution. Each Humalog Tempo Pen contains 300 units (3 millilitres). Humalog Tempo Pen is available in packs of 5 pre-filled pens or in a multiple pack containing 2 packs of 5 pre-filled pens. Not all pack sizes may be marketed. Humalog 100 units/ml contained in the pre-filled pen is the same as Humalog 100 units/ml contained in separate Humalog 100 units/ml cartridges. The pre-filled pen simply has an integrated cartridge. When the pre-filled pen is empty, you must not reuse it. The Tempo Pen contains a magnet (see section 2 “Warnings and precautions”).

Marketing Authorisation Holder
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands.

Manufacturer
Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France.

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

Belgique/België/Belgien Lietuva
Eli Lilly Benelux S.A./N.V. Eli Lilly Lietuva
Tél/Tel: + 32-(0)2 548 84 84 Tel. +370 (5) 2649600

България Luxembourg/Luxemburg
TP "Eli Lilly Nederland" B.V. - Bulgaria Eli Lilly Benelux S.A./N.V.
tel. + 359 2 491 41 40 Tél/Tel: + 32-(0)2 548 84 84

Česká republika Magyarország
ELI LILLY ČR, s.r.o. Lilly Hungária Kft.
Tel: + 420 234 664 111 Tel: + 36 1 328 5100

Danmark Malta
Eli Lilly Danmark A/S Charles de Giorgio Ltd.
Tlf: +45 45 26 6000 Tel: + 356 25600 500

Deutschland Nederland
Lilly Deutschland GmbH Eli Lilly Nederland B.V.
Tel. + 49-(0) 6172 273 2222 Tel: + 31-(0) 30 60 25 800

Eesti Norge
Eli Lilly Nederland B.V. Eli Lilly Norge A.S.
Tel: + 372 6817 280 Tlf: + 47 22 88 18 00

Ελλάδα Österreich
Farmaserv-Lilly A.E.B.E. Eli Lilly Ges. m.b.H.
Tel: +30 210 629 4600 Tel: + 43-(0) 1 711 780

España Polska
Lilly S.A. Eli Lilly Polska Sp. z o.o.
Tel: + 34-91 663 50 00 Tel: +48 22 440 33 00

France Portugal
Lilly France S.A.S. Lilly Portugal - Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: + 351-21-4126600

Hrvatska România
Eli Lilly Hrvatska d.o.o. Eli Lilly România S.R.L.
Tel: +385 1 2350 999 Tel: + 40 21 4023000

Ireland Slovenija
Eli Lilly and Company (Ireland) Limited Eli Lilly farmacevtska družba, d.o.o.
Tel: + 353-(0) 1 661 4377 Tel: +386 (0) 1 580 00 10

Ísland Slovenská republika
Icepharma hf. Eli Lilly Slovakia s.r.o.
Sími + 354 540 8000 Tel: + 421 220 663 111

Italia Suomi/Finland
Eli Lilly Italia S.p.A. Oy Eli Lilly Finland Ab
Tel: + 39- 055 42571 Puh/Tel: + 358-(0) 9 85 45 250

Κύπρος Sverige
Phadisco Ltd Eli Lilly Sweden AB
Tel: +357 22 715000 Tel: + 46-(0) 8 7378800

Latvija United Kingdom
Eli Lilly (Suisse) S.A. Pārstāvniecība Latvijā Eli Lilly and Company Limited
Tel: + 371 67364000 Tel: + 44-(0) 1256 315000

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

Instructions for use

Humalog 100 units/ml Tempo Pen injectable solution in a prefilled pen

insulin lispro

READ THESE INSTRUCTIONS BEFORE USE
Read the Instructions for Use before using insulin and each time you use another
Humalog Tempo Pen. There may be new information. These instructions do not replace
consultation with healthcare professionals regarding your medical condition or treatment.
Tempo Pen (“Pen”) is a disposable prefilled pen containing 3 mL (300 units, 100 units/mL) of
insulin. You may administer multiple doses using a single pen. The Pen allows you to
select doses in 1-unit increments. You can deliver from 1 to 60 units in a single injection. If your
dose exceeds 60 units, you will need to administer more than one injection. The plunger
moves only slightly with each injection and you may not notice the movement. The plunger
will reach the end of the cartridge only after all 300 units in the Pen have been used.
The Tempo Pen is designed to work with the Tempo Smart Button. The Tempo Smart Button is an
optional accessory that can be attached to the dose selector button of the Tempo Pen and helps
transmit Humalog dose information from the Tempo Pen to a compatible mobile application.
The Tempo Pen delivers insulin with or without the Tempo Smart Button attached. The Smart
Button must be attached to a Tempo Pen to record or transfer dose data.
Push the Smart Button straight down onto the dose selector button until you hear a click or feel it snap into place. To transmit data to the mobile application, follow the instructions provided with the Tempo Smart Button and those provided with the mobile application.
Do not share your Pen with other people, even if the needle has been changed. Do not reuse or share needles.
You could cause an infection to the person who borrowed it or get an infection from the person who borrowed it.
This Pen must not be used by blind or visually impaired individuals without assistance from someone trained to use the Pen.

Components of the Tempo Pen

Dose selector
button

How to recognize the Tempo Pen:

• Pen color: blue
• Dose selector button: burgundy (plum)
• Label: white with a burgundy (plum) colored stripe

Supplies needed for administration:

• Tempo Pen containing insulin
• Needle compatible with the Tempo Pen (BD pen needles [Becton, Dickinson and Company] are recommended)
• Alcohol swab

Needles and alcohol swabs are not included.

Preparing the Pen

• Wash your hands with soap and water.
• Check the Pen to ensure you are using the correct type of insulin. This is particularly important if you use more than one type of insulin.
• Do not use the Pen after the expiration date printed on the label. After starting to use the Pen, discard the Pen after the period of use specified in the package leaflet.
• Always use a new needle for each injection to help prevent infections and needle blockages.

Step 1:

• Remove the Pen cap.
  • Do not remove the Pen label.
• Clean the rubber closure with an alcohol swab. HUMALOG should appear clear and colorless. Do not use if it looks cloudy, colored, or contains particles.

Step 2:

• Select a new needle.
• Remove the paper protector from the outer needle cap.

Step 3:

• Attach the needle (with cap still on) straight onto the end of the Pen and rotate the needle until securely fastened.

Step 4:

• Remove the outer needle cap. Do not discard it.
• Remove the inner needle cap and discard it.

Priming the Pen
Prime the Pen before each injection.

• Priming the Pen means removing air that may have accumulated in the needle and cartridge during normal use, and ensures the Pen is working properly.
• If you do not prime before each injection, you may inject too much or too little insulin.

Step 5:

• To prime the Pen, select 2 units by rotating the dose selector button.

Step 6:

• Hold the Pen with the needle pointing upward. Gently tap the cartridge to bring air bubbles to the surface.

Step 7:

• Continue holding the Pen with the needle pointing upward. Press the dose selector button completely until it stops and an “0” appears in the dose window. Keep the dose selector button pressed and count slowly to 5. You should see insulin at the tip of the needle.

• If you do not see insulin, repeat the priming steps, but no more than 4 times.
• If you still do not see insulin, change the needle and repeat the priming steps. Small air bubbles are normal and do not affect dosing.

Selecting the Dose

• You may administer from 1 to 60 units in a single injection.
• If your dose exceeds 60 units, you will need to administer more than one injection.
  • If you need help dividing your dose correctly, ask your healthcare provider.
  • You must use a new needle for each new injection and repeat the priming step.

Step 8:

• Rotate the dose selector button to the number of units you wish to inject. The dose indicator must align with the selected dose.
  • The Pen allows selection in 1-unit increments.

• The dose selector button clicks as you rotate it.
• DO NOT count the number of clicks to determine your dose, as this may result in an incorrect dose. (Example: 12 units shown in the
• The dose can be adjusted by rotating the dose window) selector button in either direction until the correct dose is aligned with the dose indicator.

• Even numbers are printed on the dial.
• Odd numbers after 1 are shown as solid lines. (Example: 25 units shown in the dose window)
  • Always check the number in the dose window to ensure you have selected the correct dose.
  • The Pen will not allow you to select more units than are remaining in the Pen.
  • If you need to administer more units than are left in the Pen, you can:
• administer the remaining amount in the Pen and then use a new Pen to deliver the rest of your dose, or
• take a new Pen and administer the full dose.
• It is normal to see a small amount of insulin remaining in the Pen that cannot be injected.

Administering the Dose

• Inject insulin as shown to you by your healthcare provider.
• Rotate (change) your injection site with each injection.
• Do not attempt to change the dose while injecting.

Step 9:

• Choose your injection site. Insulin is injected under the skin (subcutaneously) in the abdominal area, buttocks, thighs, or upper arms.
• Clean the skin with an alcohol swab and wait for the injection site to dry before injecting the dose.

Step 10:

• Insert the needle into the skin.
• Press the dose selector button fully.
• Continue holding the

dose selector button pressed and
count slowly to 5
5 sec
before removing the needle.
Do not try to inject insulin by rotating the
dose selector button. Rotating the dose
selector button will NOT deliver your insulin dose.

Step 11:

• Remove the needle from the skin.
  • A small drop of insulin remaining at the needle tip is normal. It will not affect the delivered dose.
• Check the number shown in the dose window.
  • If you see “0” in the dose window, you have delivered the full selected dose.
  • If you do not see “0” in the dose window, do not reselect the dose. Reinsert the needle into the skin and complete the injection.
  • If you think you have not received the full amount you selected, do not restart or repeat the injection. Check your blood glucose level as instructed by your healthcare provider.
  • If you normally require 2 injections to deliver your full dose, make sure to administer the second injection. The plunger moves only slightly with each injection and you may not notice the movement. If you see blood after removing the needle from the skin, apply light pressure to the injection site with gauze or an alcohol swab. Do not rub the area.

After Injection

Step 12:

• Carefully replace the outer needle cap onto the needle.

Step 13:

• Unscrew the capped needle and dispose of it as described below (see section Disposal of the Pen and Needles).
• Do not store the Pen with the needle attached to prevent leakage, needle blockage, and air entering the cartridge.

Step 14:

• Replace the Pen cap, aligning the cap clip with the dose indicator, and press straight onto the Pen.

Disposal of the Pen and Needles

• Place used needles into a closable, puncture-resistant container such as a hard plastic container with a secure lid. Do not throw needles directly into household waste.
• Do not recycle the container once filled with needles.
• Ask your healthcare provider about available options for proper disposal of pens and this container.
• Instructions for needle handling should not replace local, institutional, or healthcare provider regulations.

Storage Instructions for the Pen

Unused Pens

• Store unused Pens in the refrigerator at a temperature between 2°C and 8°C.
• Do not freeze insulin. Do not use if it has been frozen.
• Unused Pens may be used until the expiration date printed on the label, provided they have been stored in the refrigerator.

Pen in Use

• Store the Pen you are currently using at room temperature (below 30°C), protected from dust, food, liquids, heat, and light.
• Discard the Pen you are using after the time specified in the package leaflet, even if it still contains insulin.

General Safety and Effective Use Information

• Keep the Pen and needles out of sight and reach of children.
• Do not use the Pen if any part appears broken or damaged.
• Always carry a spare Pen in case your Pen is lost or damaged.

Troubleshooting

• If you cannot remove the Pen cap, gently twist it back and forth, then pull it off.
• If you have difficulty pressing the dose selector button:
  • Pressing the dose selector button more slowly may make injection easier.
  • The needle may be blocked. Attach a new needle and prime the Pen.
  • There may be dust, food, or liquid inside the Pen. Discard the Pen and use a new one. You may need to request a new prescription from your doctor.

For further information or if you have problems with the Tempo Pen, contact your healthcare provider for
assistance or contact your local Eli Lilly branch.
Document revision date: