Label: information for the user

Mixtard 30 100UI/ml(international units/ml) injectable suspension in vial

human insulin

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

–Keep this label, as you may need to read it again.

–If you have any questions, consult your doctor, pharmacist, or nurse.

–This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

–If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

Mixtard is a human insulin with rapid and prolonged action.

Mixtard is used to reduce elevated blood sugar levels in patients with diabetes mellitus (diabetes).

Diabetes is a disease in which your body does not produce enough insulin to control blood sugar levels. Treatment with Mixtard helps to prevent diabetes complications.

Mixtard begins to reduce your blood sugar level about 30 minutes after injection and its effect lasts approximately 24 hours.

No use Mixtard

• If you are allergic to human insulin or any of the other components of this medication, see section 6.
• If you suspect you are starting to experience hypoglycemia (low blood sugar), see the Summary of Frequent and Very Frequent Adverse Reactions in section 4..
• In insulin infusion pumps.
• If the protective cap is missing or loose. All vials have a plastic safety cap. If this cap is not in perfect condition at the time of vial purchase, return it to the supplier.
• If it has not been stored correctly or has been frozen, see section 5.
• If the resuspended insulin does not have a uniformly white and turbid appearance.

If any of these circumstances occur, do not use Mixtard. Consult your doctor, pharmacist, or nurse.

Before using Mixtard

• Check the label to ensure it is the correct type of insulin.
• Remove the protective cap.
• Always use a new needle for each injection to avoid contamination.
• Needles and syringes should not be shared.

Warnings and Precautions

Some changes and activities may affect your insulin needs. Consult your doctor:

• If you have kidney, liver, adrenal, pituitary, or thyroid problems.
• If you engage in more physical exercise than usual or plan to change your usual diet, as this may affect your blood sugar level.
• If you are ill, you should continue using insulin and consult your doctor.
• If you are traveling abroad, traveling to different time zones may affect your insulin requirements and administration timing.

Changes in skin at the injection site

The injection site should be rotated to help prevent changes in fatty tissue, such as skin thickening, skin shrinkage, or lumps under the skin. Insulin may not work well if injected into an area that is swollen, shrunk, or thickened (see section 3). Inform your doctor if you notice any changes in the injection site. Inform your doctor if you are currently injecting into these affected areas, before starting to inject into a different area. Your doctor may instruct you to check your blood sugar levels more closely, and adjust your insulin or other diabetes medications.

Other medications and Mixtard

Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or may need to take any other medication.

Some medications affect your blood sugar level, and this may require adjustment of your insulin dose. The following medications are commonly used and may affect your insulin treatment:

Your blood sugar level may decrease (hypoglycemia) if you take:

•Other diabetes medications

•Monamine oxidase inhibitors (MAOIs) (used to treat depression)

•Beta-blockers (used to treat high blood pressure)

•Angiotensin-converting enzyme inhibitors (ACE inhibitors) (used to treat certain heart conditions or high blood pressure)

•Salicylates (used to relieve pain and reduce fever)

•Anabolic steroids (such as testosterone)

•Sulfonamides (used to treat infections)

Your blood sugar level may increase (hyperglycemia) if you take:

•Oral contraceptives (birth control pills)

•Thiazides (used to treat high blood pressure or fluid retention)

•Glucocorticoids (such as cortisone, used to treat inflammation)

•Thyroid hormone (used to treat thyroid gland disorders)

•Sympathomimetics (such as epinephrine [adrenaline], salbutamol, or terbutaline, used to treat asthma)

•Growth hormone (a medication that stimulates bone and somatic growth and has a significant impact on the body's metabolic processes)

•Danazol (a medication that acts on ovulation)

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder that typically occurs in middle-aged adults, caused by excessive production of growth hormone in the pituitary gland) may increase or decrease blood sugar levels.

Beta-blockers (used to treat high blood pressure) may weaken or completely suppress the early warning signs that help recognize low blood sugar levels.

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with long-standing type 2 diabetes and pre-existing heart disease or 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 unusual shortness of breath, rapid weight gain, or localized inflammation (edema).

If you have taken any of the medications listed, inform your doctor, pharmacist, or nurse.

Use of Mixtard with alcohol

?If you drink alcohol, your insulin needs may change, as your blood sugar level may increase or decrease. It is recommended to follow a strict control.

Pregnancy and lactation

?If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication. Mixtard can be used during pregnancy.You may need to adjust your insulin dose during pregnancy and after delivery. Strict control of diabetes, especially to prevent hypoglycemia, is essential for your baby's health.

?No restrictions apply to Mixtard treatment during lactation.

Consult your doctor, pharmacist, or nurse before using this medication during pregnancy or lactation.

Driving and operating machinery

?Ask your doctor if you can drive vehicles or operate machinery:

•If you experience frequent episodes of hypoglycemia.

•If you find it difficult to recognize the symptoms of hypoglycemia.

If your blood sugar level is high or low, it may affect your concentration and reaction time, and therefore also your ability to drive or operate machinery. Be aware that you may put yourself or others at risk.

Mixtard contains sodium

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

Dosage and When to Use Insulin

Follow exactly the administration instructions of this medication and the doses indicated by your doctor. In case of doubt, consult your doctor, pharmacist, or nurse again.

Take foods containing carbohydrates within 30 minutes after the injection to prevent a drop in blood sugar levels.

Do not change insulin unless your doctor tells you to. If your doctor changes you from one type or brand of insulin to another, you may need to adjust your dose.

Use in Children and Adolescents

Mixtard can be used in children and adolescents.

Use in Special Patient Groups

If you have kidney or liver failure or if you are over 65 years old, you must check your blood sugar levels more frequently and talk to your doctor about possible changes in insulin dose.

How and Where to Inject Insulin

Mixtard is administered by subcutaneous injection under the skin. Never inject directly into a vein (intravenous injection) or muscle (intramuscular injection).

With each injection, change the injection site within the designated skin area. This may reduce the risk of developing skin lumps and depressions, see section 4. The best areas for injection are the following: the front of the waist (abdomen), the gluteal region, the front of the thigh, or the upper arm. The effect of insulin will be faster if the injection is made in the waist (abdomen). You must measure your blood sugar levels regularly.

How to Use Mixtard

Mixtard vials must be used with insulin syringes graduated with the corresponding unit scale.

1.Shake the vial between your hands until the liquid has a uniformly white and turbid appearance. Resuspension will be easier when the insulin has reached room temperature.

2.Insert the same amount of air into the syringe as the insulin dose to be injected. Inject the air into the vial.

3.Turn the vial and syringe around and extract the correct dose of insulin from the syringe. Remove the needle from the vial. Then, expel the air from the syringe and check that the dose is correct.

How to Inject Mixtard

• Insulin must be injected under the skin. Use the injection technique advised by your doctor or nurse.
• Keep the needle under the skin for at least 6 seconds to ensure that all the insulin has been injected.
• Dispose of the needle and syringe after each injection.

If You Use More Insulin Than You Should

If you use too much insulin, your blood sugar levels will drop too low (hypoglycemia). See Severe and Very Common Adverse Reactions in section 4.

If You Forget to Use Insulin

If you forget to use insulin, your blood sugar levels may rise too high (hyperglycemia). See Diabetes-Related Effects in section 4.

If You Stop Using Insulin

Do not stop using insulin without talking to your doctor first, who will explain what you should do. Stopping insulin may cause severe hyperglycemia and ketoacidosis. See Diabetes-Related Effects in section 4.

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

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

Summary of serious and very common side effects

Hypoglycemia (low blood sugar)is a very common side effect. It can affect more than 1 in 10people.

The blood sugar level can drop if:

•Too much insulin is injected.

•Very little food is eaten or a meal is skipped.

•More physical exercise than usual is done.

•Alcohol is consumed, see Use of Mixtard with alcohol in section 2.

Signs of low blood sugar:chills, cold and pale skin, headache, rapid heartbeat, feeling unwell, excessive appetite, temporary visual disturbances, drowsiness, fatigue and weakness, nervousness or tremors, anxiety, confusion, difficulty concentrating.

A severe drop in blood sugar can lead to loss of consciousness. If not treated, it can cause brain damage (temporary or permanent) and even death. You can regain consciousness more quickly if someone who knows how to administer it gives you a glucagon injection. If you are given glucagon, you should also take glucose or a high-sugar product as soon as you regain consciousness. If you do not respond to glucagon treatment, you will need to receive treatment in a hospital.

What to do if you experience low blood sugar:

?If you experience low blood sugar, take glucose tablets or another high-sugar product (such as candy, cookies, or fruit juice). If possible, measure your blood sugar level and rest. Always carry glucose tablets or high-sugar products with you, just in case.

?When the symptoms of low blood sugar have disappeared or your blood sugar level has stabilized, continue with insulin treatment as usual.

?If your blood sugar level is so low that you faint, if you have needed a glucagon injection, or if you have had many episodes of low blood sugar, talk to your doctor. You may need to adjust the dose or frequency of insulin, your eating habits, or exercise.

Inform relevant people that you have diabetes and what the consequences may be, such as the risk of fainting (loss of consciousness) due to low blood sugar. Let them know that if you faint, they should turn you on your side and seek medical help immediately. Do not give you food or drinks, as you may choke.

Thesevere allergic reactionto Mixtard or one of its components (called a systemic allergic reaction) is a very rare but potentially life-threatening side effect. It can affect up to 1 in 10,000people.

Consult your doctor immediately:

•If allergy symptoms spread to other parts of the body.

•If you suddenly feel unwell and have sweating, feeling unwell (vomiting), difficulty breathing, rapid heartbeat, or dizziness.

?If you notice any of these symptoms, seek medical help immediately.

Changes in skin at the injection site: If insulin is injected in the same place, the fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy) (this can affect up to 1 in 100 people). Bumps under the skin can also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis; it is not known how often this occurs). Insulin may not work well if injected in a thickened, shrunk, or swollen area. Change the injection site to help prevent these skin changes.

List of other side effects

Less common side effects

They can affect up to 1 in 100people.

Allergic symptoms: local allergic reactions (pain, redness, rashes, inflammation, hematomas, swelling, and itching) can occur at the injection site. They usually disappear within a few weeks of starting insulin treatment. If they do not disappear or spread to the entire body, you should consult your doctor immediately. Also see the severe allergic reactions mentioned earlier.

Diabetic retinopathy(eye disease related to diabetes that can cause vision loss): if you have diabetic retinopathy and your blood sugar level improves rapidly, the retinopathy may worsen. In this case, you should consult your doctor.

Joint inflammation: when starting insulin treatment, fluid accumulation can cause joint inflammation, particularly in the ankles and other joints. This effect usually disappears quickly. If it does not, consult your doctor.

Painful neuropathy(pain due to nerve damage): if your blood sugar level improves rapidly, you may experience pain related to nerves. This is known as acute painful neuropathy and is usually transient.

Rare side effects

They can affect up to1 in10,000people.

Visual problems: when starting insulin treatment, your vision may be affected, but it is usually temporary.

Reporting side effects

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

Effects related to diabetes

High blood sugar (hyperglycemia)

You may experience high blood sugar if:

•Not enough insulin is injected.

•You forget to inject insulin or stop using it.

•You inject less insulin than you need.

•You have an infection and/or fever.

•You eat more than usual.

•You do less physical exercise than usual.

Warning signs of high blood sugar:

Warning signs appear gradually and include frequent urination, thirst, loss of appetite, feeling unwell (nausea or vomiting), drowsiness or fatigue, dry and red skin, dry mouth, and fruity breath (acetone).

What to do if you experience high blood sugar:

?If you experience any of the symptoms described above: check your blood sugar level and the presence of ketones in your urine if possible, and then consult your doctor immediately.

?They may be symptoms of a severe condition called diabetic ketoacidosis (formation of acid in the blood due to the body breaking down fat instead of sugar). If not treated, it could cause diabetic coma and even death.

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

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

Before opening:store in refrigerator (between 2°C and 8°C). Keep away from the refrigerator element. Do not freeze.

During use or when carrying a spare:do not refrigerate or freeze. It can be carried and stored at room temperature (below 25ºC) for up to 6weeks.

Always store the vial in the outer packaging, when not in use, to protect it from light.

Dispose of the needle and syringe after each injection.

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

Composition of Mixtard 30

–The active principle is human insulin. Mixtard is a mixture composed of 30% human insulin soluble and 70% human insulin isophane. Each ml contains 100 UI of human insulin. Each vial contains 1,000 UI of human insulin in 10 ml of injectable suspension.

–The other components are zinc chloride, glycerol, metacresol, phenol, disodium dihydrogen phosphate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injectable preparations.

Appearance of the product and contents of the container

Mixtard is presented as an injectable suspension. After resuspension, the liquid must have a uniformly white and turbid appearance.

Container sizes of 1 or 5 vials of 10 ml or multiple container of 5 containers of 1 vial of 10 ml. Some container sizes may only be marketed.

The suspension is aqueous, white, and turbid in appearance.

Holder of the marketing authorization

Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark

Responsible for manufacturing

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd, Denmark

Novo Nordisk Production SAS

45, Avenue d'Orléans

F-28000 Chartres, France

Date of the last review of this leaflet:

Other sources of information

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