Mixtard 30 100 IU/ml suspension for injection in vial

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

human insulin

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, pharmacist or nurse.
• 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, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

1. What Mixtard is and what it is used for

Mixtard is a human insulin with both rapid-acting and prolonged action.

Mixtard is used to lower elevated blood glucose levels in patients with diabetes mellitus (diabetes).

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

Mixtard begins to lower your blood glucose level about 30 minutes after injection, and its effect lasts for approximately 24 hours.

2. What you need to know before using Mixtard

Do not use Mixtard

• If you are allergic to human insulin or to any of the other components of this medicine, see section 6.
• If you suspect you are beginning to experience hypoglycaemia (low blood sugar levels), see Summary of serious and very common adverse effects in section 4.
• In insulin infusion pumps.
• If the protective cap is missing or loose. All vials have a plastic safety seal cap. If this is not intact at the time of purchase, return the vial to your supplier.
• If it has not been stored correctly or has been frozen, see section 5.
• If the resuspended insulin does not appear uniformly white and cloudy.

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

Before using Mixtard

• Check the label to make sure 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 must not be shared.

Warnings and precautions

Certain conditions and activities may affect your insulin requirements. Consult your doctor:

• If you have problems with your kidneys, liver, adrenal glands, pituitary gland, or thyroid gland.
• If you are doing more physical exercise than usual or wish to change your normal diet, as this may affect your blood sugar levels.
• If you are ill, you must continue using insulin and consult your doctor.
• If you are travelling abroad, travelling across time zones may affect your insulin requirements and the timing of administration.

Skin changes at the injection site

Injection sites should be rotated to help prevent changes in fatty tissue, such as thickening of the skin, skin shrinkage, or lumps under the skin. Insulin may not work as well if injected into a lumpy, shrunken, or thickened area (see section 3). Inform your doctor if you notice any changes at the injection site. Inform your doctor if you are currently injecting into these affected areas 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 that of your other antidiabetic medications.

Other medicines and Mixtard

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

Some medicines affect your blood sugar levels, which may require adjustment of your insulin dose. Listed below are the most common medicines that may affect your insulin treatment.

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

• Other medicines for the treatment of diabetes
• Monoamine 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)
• Sulphonamides (used to treat infections).

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

• Oral contraceptives (birth control pills)
• Thiazides (used to treat high blood pressure or excessive 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 medicine used to stimulate bone and somatic growth and with significant influence on the body's metabolic processes)
• Danazol (a medicine that affects ovulation).

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

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

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with long-standing type 2 diabetes and 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 unusual shortness of breath, rapid weight gain, or localized swelling (oedema).

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

Use of Mixtard with alcohol

? If you drink alcohol, your insulin requirements may change, as blood sugar levels may increase or decrease. Strict monitoring is recommended.

Pregnancy and breastfeeding

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

? There are no restrictions on the use of Mixtard during breastfeeding.

Consult your doctor, pharmacist, or nurse before using this medicine during pregnancy or breastfeeding.

Driving and using machines

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

• If you experience frequent episodes of hypoglycaemia.
• If you have difficulty recognizing the symptoms of hypoglycaemia.

If your blood sugar level is too high or too low, it may affect your concentration and reaction ability, and therefore your ability to drive or operate machinery. Bear in mind that you may be putting yourself or others at risk.

Mixtard contains sodium

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

3. How to use Mixtard

Dosage and when to use insulin

Follow exactly the instructions for use and dosage of this medicine as given by your doctor. If in doubt, consult your doctor, pharmacist, or nurse again.

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

Do not switch insulin unless instructed by your doctor. If your doctor changes your type or brand of insulin, 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 renal or hepatic impairment or are over 65 years of age, you should check your blood sugar level more frequently and discuss possible dose adjustments with your doctor.

How and where to inject insulin

Mixtard is administered by injection under the skin (subcutaneous administration). It must never be injected directly into a vein (intravenous injection) or into muscle (intramuscular injection).

With each injection, change the injection site within the area of skin you are using. This may reduce the risk of developing lumps and dents in the skin; see section 4. The best areas for injection are: the front of the waist (abdomen), the buttocks, the front of the thigh, or the upper arm. The insulin effect will be faster if injected into the waist (abdomen). You should measure your blood sugar level regularly.

How to use Mixtard

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

1. Roll the vial between your hands until the liquid appears uniformly white and cloudy. Resuspension will be easier when the insulin has reached room temperature.
2. Draw into the syringe the same amount of air as the dose of insulin to be injected. Inject the air into the vial.
3. Turn the vial and syringe upside down and withdraw the correct dose of insulin into 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 should be injected under your 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 level will drop too low (hypoglycaemia). See Summary of serious and very common adverse effects in section 4.

If you forget to use the insulin

If you forget to use your insulin, your blood sugar level may rise too high (hyperglycaemia). See Effects arising from diabetes in section 4.

If you stop using insulin

Do not stop using insulin without first talking to your doctor, who will advise you on what to do. Stopping insulin may cause excessive increase in blood sugar levels (severe hyperglycaemia) and ketoacidosis. See Effects arising from diabetes in section 4.

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

4. Possible adverse effects

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

Summary of serious and very common adverse effects

A drop in blood sugar level (hypoglycaemia) is a very common adverse effect. It may affect more than 1 in 10 people.

Your blood sugar level may drop if:

• You inject too much insulin.
• You eat very little or skip a meal.
• You do more physical exercise than usual.
• You drink alcohol – see Use of Mixtard with alcohol in section 2.

Signs of low blood sugar: cold sweating, cold and pale skin, headache, rapid heartbeat, feeling unwell, excessive hunger, temporary visual disturbances, drowsiness, unusual tiredness and weakness, nervousness or trembling, anxiety, confusion, difficulty concentrating.

A severe drop in blood sugar can lead to loss of consciousness. If untreated, it may cause brain damage (temporary or permanent) and even death. You may regain consciousness more quickly if someone who knows how to do it administers a glucagon injection. If glucagon is given, you should also take glucose or a sugary product as soon as you regain consciousness. If there is no response to glucagon treatment, you will need to be treated 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 (for example, sweets, biscuits, fruit juice). If possible, check your blood sugar level and rest. Always carry glucose tablets or high-sugar products with you, just in case.

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

? If your blood sugar level is so low that you lose consciousness, if you required a glucagon injection, or if you have had several episodes of low blood sugar, speak to your doctor. You may need to adjust your insulin dose or frequency, eating habits, or exercise routine.

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 onto your side and seek immediate medical help. They should not give you food or drink, as you could choke.

Severe allergic reaction to Mixtard or one of its components (called systemic allergic reaction) is a very rare adverse effect, but it can be life-threatening. It may affect up to 1 in 10,000 people.

Contact 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.

Skin changes at the injection site: If you inject insulin in the same place repeatedly, fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy) (may affect up to 1 in 100 people). Lumps under the skin may also occur due to accumulation of a protein called amyloid (cutaneous amyloidosis; frequency unknown). Insulin may not work well if injected into a lumpy, shrunken, or thickened area. Change your injection site regularly to help prevent these skin changes.

List of other adverse effects

Uncommon adverse effects

May affect up to 1 in 100 people.

Allergy symptoms: Local allergic reactions (pain, redness, rash, swelling, bruising, swelling, and itching) may occur at the injection site. These usually disappear within a few weeks of starting insulin treatment. If they do not disappear or spread to the whole body, you must contact your doctor immediately. See also the information on severe allergic reactions mentioned above.

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

Joint swelling: when starting insulin treatment, fluid retention may cause swelling of 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 improves very rapidly, you may experience nerve-related pain. This is known as acute painful neuropathy and is usually temporary.

Very rare adverse effects

May affect up to 1 in 10,000 people.

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

Effects arising from diabetes

High blood sugar level (hyperglycaemia)

You may experience a high blood sugar level if:

• You have not injected enough insulin.
• You forget to inject insulin or stop using it.
• You repeatedly 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 symptoms appear gradually and include frequent urination, thirst, loss of appetite, feeling unwell (nausea or vomiting), drowsiness or tiredness, dry and flushed skin, dry mouth, and fruity breath (acetone).

What to do if blood sugar rises:

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

? These may be symptoms of a very serious condition called diabetic ketoacidosis (build-up of acid in the blood due to the body breaking down fat instead of sugar). If untreated, it could lead to diabetic coma and even death.

5. Storage of Mixtard

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

Do not use this medicine after the expiry date which is stated on the label of the vial and on the packaging after EXP. The expiry date refers to the last day of the month indicated.

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

During use or when carried as a spare: do not refrigerate or freeze. May be carried on the person and stored at room temperature (below 25°C) for up to 6 weeks.

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

Dispose of the needle and syringe after each injection.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Mixtard 30

• The active substance is human insulin. Mixtard is a mixture consisting of 30% soluble human insulin and 70% isophane human insulin. Each ml contains 100 IU of human insulin. Each vial contains 1,000 IU of human insulin in 10 ml of injectable suspension.
• The other components are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injections.

Appearance of the product and contents of the pack

Mixtard is presented as an injectable suspension. After resuspension, the liquid should appear uniformly white and cloudy.

Pack sizes of 1 or 5 vials of 10 ml or multiple pack of 5 packs of 1 vial of 10 ml. Only some pack sizes may be marketed.

The suspension is aqueous, white and cloudy in appearance.

Marketing Authorisation Holder

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

Manufacturer

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 latest revision of this leaflet:

Other sources of information

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