Humalog Mix50 Kwikpen 100 U/ml injection suspension

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Humalog Mix50 100 units/ml injection suspension in cartridge

insulin lispro

Please read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Humalog Mix50 is and what it is used for
2. What you need to know before you use Humalog Mix50
3. How to use Humalog Mix50
4. Possible side effects
5. 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 to treat diabetes. Humalog Mix50 is a premixed suspension. Its active substance is insulin lispro. In Humalog Mix50, 50% of insulin lispro is dissolved in water and works more rapidly than regular human insulin because the insulin molecule has been slightly modified. In Humalog Mix50, 50% of insulin lispro is combined with protamine sulfate in suspension to prolong its action.

You have diabetes when your pancreas does not produce enough insulin to control the glucose level in your blood. Humalog Mix50 acts as a replacement for your own insulin and is used to control glucose levels over the long term. Humalog Mix50 acts very rapidly and for a longer duration than soluble insulin. Normally, you should take Humalog Mix50 within 15 minutes around a meal.

Your doctor may recommend that you use Humalog Mix50 together with a longer-acting insulin. Each of these comes with its own package leaflet containing specific information. Do not change your insulin unless your doctor tells you to do so. Exercise great caution when switching from one 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). How to manage mild hypoglycaemia is explained later in this leaflet (see Section 3: If you use more Humalog Mix50 than you should).
• If you are allergic to insulin lispro or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

• Always check at the pharmacy the name and type of insulin shown on the packaging and cartridge label. Make sure you are receiving the Humalog Mix50 prescribed by your doctor.
• If your blood sugar levels are well controlled with your current insulin therapy, you may not notice the warning symptoms that alert you when your blood sugar is dropping too low. These warning symptoms are described later in this leaflet. You must carefully plan your meal times, exercise schedule, and the extent of physical activity. You should also monitor your blood sugar levels closely by frequently testing your blood glucose.
• Some patients who experienced hypoglycaemia after switching from animal insulin to human insulin have reported that early warning symptoms were less noticeable or different. If you experience frequent hypoglycaemia or have difficulty recognizing it, please inform your doctor.
• If you answer YES to any of the following questions, discuss it with your doctor, pharmacist, or diabetes educator.

? Have you recently become ill?

? Do you have liver or kidney problems?

? Are you exercising more than usual?

• Your insulin requirement may change if you consume alcohol.
• If you are planning to travel abroad, inform your doctor, pharmacist, or diabetes educator. Time differences between countries may require you to adjust your injection and meal schedule compared to your routine at home.
• Some patients with long-standing type 2 diabetes and pre-existing heart disease or prior stroke, who were treated with pioglitazone and insulin, developed heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as difficulty breathing, rapid weight gain, or localized swelling (oedema).

Skin changes at the injection site

Rotate your injection sites to avoid skin changes such as lumps under the skin. Insulin may not work effectively if injected into an area with lumps (see How to use Humalog Mix50). Contact your doctor if you are currently injecting into a lumpy area before switching to a different site. Your doctor may advise you to monitor your blood sugar levels more closely and adjust your insulin dose or other antidiabetic medications.

Other medicines and Humalog Mix50

Your insulin requirements may change if you are taking:

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

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

Pregnancy and breastfeeding

Are you pregnant or planning to become pregnant? Are you breastfeeding? Your insulin requirement generally decreases during the first three months of pregnancy and increases during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet. If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

Your ability to concentrate or react may be reduced if you experience hypoglycaemia. Be aware of this potential problem, considering all situations that could pose a risk to yourself or others (e.g. driving a vehicle or operating machinery). Consult your doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia
• have difficulty perceiving or do not perceive symptoms of hypoglycaemia

Humalog Mix50 contains sodium

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

3. How to use Humalog Mix50

The 3 ml cartridges are for exclusive use in Lilly 3 ml insulin pens. They must not be used in 1.5 ml pens.

Always follow exactly the dosing instructions for this medicine given by your doctor. If in doubt, consult your doctor again. To prevent possible transmission of disease, each cartridge must be used only by you, even if the needle of the device is changed.

Dosage

• Humalog Mix50 should normally be injected within 15 minutes around a meal. If necessary, it may be injected shortly after a meal. However, your doctor has specifically instructed you on exactly how much to use, when to take it, and how often. These instructions are specific to you. Follow them precisely and attend your diabetes clinic regularly.
• If you switch the type of insulin you use (for example, from animal or human insulin to a product containing Humalog Mix50), you may need to use a larger or smaller amount than before. This may apply only for the first injection, or it may require a gradual adjustment lasting several weeks or months.
• Inject Humalog Mix50 under the skin. Do not use any other route of administration. Under no circumstances should Humalog Mix50 be administered intravenously.

How to prepare Humalog Mix50

• The cartridges containing Humalog Mix50 must be rolled between the palms of the hands ten times and inverted 180° another ten times immediately before use to resuspend the insulin, until the appearance is uniformly cloudy or milky. If not, repeat the above procedure until the components are fully mixed. The cartridges contain a small glass bead to aid mixing. Do not shake vigorously, as foam may form, which could interfere with accurate dose measurement. Examine the cartridges frequently and do not use them if clumps or solid white particles adhering to the bottom or sides of the cartridge are visible, giving it a frost-like appearance. Check this each time before injecting.

How to prepare the pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• Use Humalog Mix50 cartridges only with Lilly insulin pens. Make sure the pen’s instruction leaflet refers to Humalog or Lilly cartridges. The 3 ml cartridges fit only in 3 ml pens.
• Follow the instructions provided with the pen. Insert the cartridge into the pen.
• Set the dose to 1 or 2 units. Then hold the pen with the needle pointing upward and tap the side gently so that any air bubble rises to the top. While keeping the pen upward, press the injection mechanism. Hold it down until a drop of Humalog Mix50 appears at the needle tip. Small air bubbles may still remain in the pen. These are harmless, but if the air bubble is too large, the injected dose may be less accurate.

How to inject Humalog Mix50

• Before injecting, clean your skin as you have been taught. Inject under the skin as instructed. Do not inject directly into a vein. After injection, leave the needle in the skin for five seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure to inject at least 1 cm away from the previous injection site and rotate your injection sites as instructed.

After injection

• Immediately after completing the injection, remove the needle from the pen using the needle’s outer cap. This keeps the Humalog Mix50 sterile and prevents leakage. It also avoids air entering the pen and needle blockage. Do not share needles. Do not share your pen. Replace the cap on the pen. Leave the cartridge inside the pen.

Subsequent injections

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

Do not mix any other insulin into a Humalog Mix50 cartridge. Once the cartridge is empty, it cannot be reused.

If you use more Humalog Mix50 than you should

If you use more Humalog Mix50 than needed or are unsure how much you have injected, you may experience low blood sugar (hypoglycemia). Check your blood glucose level.

If your blood sugar is low (mild hypoglycemia), take glucose tablets, sugar, or a sugary drink. Then eat fruit, biscuits, or a snack as instructed by your doctor, and rest afterward. This usually helps overcome mild hypoglycemia or a small insulin overdose. If your condition worsens and your breathing becomes shallow and your skin turns pale, call your doctor immediately. Severe hypoglycemia may be treated with a glucagon injection. After a glucagon injection, glucose or sugar should be taken. If there is no response to glucagon, you must go to the hospital. Ask your doctor for information about glucagon.

If you forget to use Humalog Mix50

If you use less Humalog Mix50 than needed or are unsure how much you have injected, you may experience high blood sugar (hyperglycemia). Check your blood glucose level.

If not properly treated, 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 A and B in section 4 “Possible side effects”).

Three simple measures to avoid hypoglycemia or hyperglycemia are:

• Always keep spare pens and cartridges in case you lose or damage them.
• Always carry some form of identification indicating you are diabetic.
• Always carry some sugar with you.

If you stop using Humalog Mix50

If you use less Humalog Mix50 than needed, you may experience high blood sugar. Do not switch insulin unless instructed by your doctor.

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

4. Possible adverse effects

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

Systemic allergy is rare (≥1/10,000 to <1/1,000). It presents the following symptoms:

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

Local allergy is common (≥ 1/100 to <1/10). In some people, the area where insulin has been injected becomes red, swollen, or itchy. This condition usually disappears within a few days or weeks. If this happens to you, discuss it with your doctor.

Lipodystrophy is uncommon (≥ 1/1,000 to <1/100). If you inject insulin too frequently in the same spot, the fatty tissue may shrink (lipoatrophy) or thicken (lipohypertrophy). Lumps under the skin may also occur due to accumulation of a protein called amyloid (cutaneous amyloidosis). Insulin may not work as well if injected into a lumpy area. Change your injection site regularly to help prevent these skin changes.

Cases of edema (for example, swelling in the arms, ankles; fluid retention) have been reported, particularly at the beginning of insulin treatment or during changes in treatment aimed at improving blood sugar control.

Reporting of adverse reactions

If you experience any adverse reactions, consult your doctor or pharmacist, even if they are possible adverse reactions not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

Common diabetes-related problems

1. Hypoglycemia

Hypoglycemia (low blood sugar) means you have too little sugar in your blood.

It can be caused by:

• injecting too much Humalog Mix50 or any other type of insulin;
• skipping a meal, delaying a meal, or changing your diet;
• doing excessive work or physical exercise immediately before or after a meal;
• having an infection or being ill (especially diarrhea or vomiting);
• changes in your insulin requirements; or
• worsening of kidney or liver disease.

Alcohol and certain medications can affect your blood sugar levels.

The first symptoms of low blood sugar usually appear suddenly and include:

Until you are certain you recognize the warning symptoms, avoid situations (e.g., driving a car) where you or others might be endangered if hypoglycemia occurs.

1. Hyperglycemia and diabetic ketoacidosis

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

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

Hyperglycemia can lead to diabetic ketoacidosis. The initial symptoms develop slowly over several hours or days. These symptoms include:

Severe symptoms are labored breathing and rapid pulse. Seek immediate medical assistance.

1. Illnesses

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

5. Storage of Humalog Mix50

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

Store the cartridge in use at room temperature (below 30ºC) and discard it after 28 days. Do not place it near any heat source or expose it to direct sunlight. Do not store your pen or the cartridges you are using in the refrigerator. The pen with the cartridge inserted must not be stored with the needle attached.

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

Do not use this medicine after the 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 clumps or solid white particles adhering to the bottom or sides of the cartridge, giving it a frost-like appearance. Check this each time before injecting.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of unused medicines and their containers. This helps protect the environment.

6. Contents of the pack and other information

Composition of Humalog Mix50 100 units/ml injectable suspension in cartridge

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

Appearance of the product and contents of the pack

Humalog Mix50 100 units/ml injectable suspension is a sterile, white suspension containing 100 units of insulin lispro per milliliter of injectable suspension (100 units/ml). In Humalog Mix50, 50% of insulin lispro is dissolved in water. The remaining 50% of insulin lispro is suspended together with protamine sulfate. Each cartridge contains 300 units (3 milliliters). The packs contain either 5 or 10 cartridges. Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

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

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

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

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder:

Date of the latest review of this leaflet:

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