Apidra 100 units/ml solution for injection in cartridge

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Apidra 100 Units/ml solution for injection in cartridge

Insulin glulisine

Read this entire leaflet carefully before you start using this medicine because it contains important information for you. Instructions for use of the insulin pen are provided with your insulin pen. Please consult them before using your medicine.

• 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, including any adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Apidra is and what it is used for

Apidra is an antidiabetic agent used to reduce high blood sugar levels in patients with diabetes mellitus. It can be administered to adults, adolescents, and children aged 6 years and older. Diabetes mellitus is a condition in which your body does not produce enough insulin to control blood sugar levels.

It is produced by biotechnology. It has a rapid onset of action within 10–20 minutes and a short duration of action of approximately 4 hours.

2. What you need to know before using Apidra

Do not use Apidra

• If you are allergic to insulin glulisine or to any of the other ingredients of this medicine (listed in section 6).
• If your blood sugar level is too low (hypoglycemia), follow the hypoglycemia guidance (see the box at the end of this leaflet).

Warnings and precautions

Apidra in cartridges is intended only for subcutaneous injection using a reusable pen (see also section 3). Please consult your doctor if you need to administer insulin by another method.

Talk to your doctor, pharmacist, or nurse before starting to use Apidra.

Carefully follow the dosage instructions, monitoring (blood tests), diet, and physical activity (physical work and exercise) as directed by your doctor.

Special patient groups

If you have liver or kidney problems, consult your doctor, as you may require a lower dose.

There is insufficient clinical information on the use of Apidra in children under 6 years of age.

Skin changes at the injection site.

Rotate your injection sites to avoid skin changes such as lumps under the skin. Insulin may not work well if injected into an area with lumps (see How to use Apidra). 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 that of your other antidiabetic medications.

Travel

Before traveling, consult your doctor. You may need advice on:

• the availability of your insulin in the country you are visiting,
• supplies of insulin, needles, etc.,
• proper storage of insulin during travel,
• meal times and insulin administration schedules during travel,
• possible effects of crossing time zones,
• potential new health risks in the countries you are visiting,
• what to do in emergency situations if you become ill.

Illness and injury

Managing your diabetes may require special care in the following situations:

• If you are ill or suffer a major injury, your blood sugar level may rise (hyperglycemia).
• If you do not eat enough, your blood sugar level may drop too low (hypoglycemia). In most cases, you will need medical attention. Be sure to consult a doctor immediately.

If you have type 1 diabetes (insulin-dependent diabetes mellitus), do not stop taking your insulin or fail to consume sufficient carbohydrates. Always inform healthcare providers involved in your care that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and prior heart disease or stroke who were treated with pioglitazone and insulin developed heart failure. Inform your doctor as soon as possible if you experience symptoms of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).

Using Apidra with other medicines

Some medicines can alter your blood sugar levels (increase, decrease, or both, depending on the situation). In each case, your insulin dose may need to be adjusted to avoid blood sugar levels that are either too low or too high. Exercise caution when starting or stopping any other medication.

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicine. Ask your doctor before taking any medicine whether it could affect your blood sugar level and what steps you should take, if any.

Medicines that may cause a decrease in your blood sugar level (hypoglycemia) include:

• all other medicines for treating diabetes,
• angiotensin-converting enzyme (ACE) inhibitors (used to treat certain heart conditions or hypertension),
• disopyramide (used to treat certain heart conditions),
• fluoxetine (used to treat depression),
• fibrates (used to reduce high blood lipid levels),
• monoamine oxidase (MAO) inhibitors (used to treat depression),
• pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• antibiotics of the sulfonamide group.

Medicines that may cause an increase in your blood sugar level (hyperglycemia) include:

• corticosteroids (such as "cortisone," used to treat inflammation),
• danazol (a medication that affects ovulation),
• diazoxide (used to treat hypertension),
• diuretics (used to treat hypertension or fluid retention),
• glucagon (a pancreatic hormone used to treat severe hypoglycemia),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (such as oral contraceptives used for birth control),
• phenothiazine derivatives (used to treat psychiatric disorders),
• somatropin (growth hormone),
• sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline, used to treat asthma),
• thyroid hormones (used to treat thyroid gland disorders),
• protease inhibitors (used to treat HIV),
• atypical antipsychotic medicines (such as clozapine and olanzapine).

Your blood sugar level may rise or fall if you take:

• beta-blockers (used to treat hypertension),
• clonidine (used to treat hypertension),
• lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat certain parasitic infections) may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

Beta-blockers, as well as other sympatholytic medicines (such as clonidine, guanethidine, and reserpine), may weaken or completely suppress the early warning symptoms that help you recognize hypoglycemia.

If you are unsure whether you are taking any of these medicines, ask your doctor or pharmacist.

Using Apidra with alcohol

Your blood sugar levels may rise or fall if you drink alcohol.

Pregnancy and breastfeeding

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.

Inform your doctor if you are planning to become pregnant or are already pregnant. Your insulin dose may need adjustment during pregnancy and after delivery. Careful diabetes control and prevention of hypoglycemia are important for your baby's health.

There are no data or the data are limited regarding the use of Apidra in pregnant women.

If you are breastfeeding, consult your doctor, as you may require adjustments to your insulin doses and diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

• you have hypoglycemia (low blood sugar),
• you have hyperglycemia (high blood sugar).

Be aware of this potential problem and consider all situations that could pose a risk to yourself or others (such as driving or operating machinery).

You should ask your doctor for advice about your ability to drive if:

• you have frequent episodes of hypoglycemia,
• your early warning symptoms of hypoglycemia are reduced or absent.

Important information about some of the ingredients of Apidra

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

Apidra contains metacresol

Apidra contains metacresol, which may cause allergic reactions.

3. How to use Apidra

Dosage

Follow exactly the instructions given by your doctor for using this medicine. If in doubt, consult your doctor or pharmacist again.

Your doctor will determine the dose of Apidra you need based on your lifestyle, blood glucose (sugar) monitoring results, and your previous insulin treatment.

Apidra is a short-acting insulin. Your doctor may instruct you to use it in combination with an intermediate-acting insulin, long-acting insulin, a basal insulin, or with tablets used to treat high blood sugar levels.

If you are switching from another insulin to insulin glulisine, your doctor may need to adjust your dose.

Many factors can influence your blood sugar levels. You should be aware of these factors so you can respond appropriately to changes in your blood sugar levels and prevent them from becoming too high or too low. See the box at the end of this leaflet for more information.

Method of administration

Apidra is injected under the skin (subcutaneously).

Your doctor will advise you on which area of skin to inject Apidra. Apidra may be injected into the abdominal wall, thigh, or upper arm, or administered by continuous infusion into the abdominal wall. The effect will be slightly faster if insulin is injected into the abdomen. As with all other insulins, injection and infusion sites within an injection area (abdomen, thigh, or upper arm) should be rotated from one injection to the next.

Frequency of administration

Apidra should be administered shortly (0–15 minutes) before or shortly after meals.

Instructions for correct use

How to handle cartridges

Apidra in cartridges is intended only for subcutaneous injection using a reusable pen. Consult your doctor if you need to inject insulin by another method.

To ensure you receive the exact dose, Apidra cartridges must only be used with the following pens:

• JuniorSTAR, which delivers doses in 0.5 unit increments
• ClikSTAR, Tactipen, Autopen 24, AllStar, or AllStar PRO, which deliver doses in 1 unit increments.

In your country, only some of these pens may be available.

The pen must be used as recommended in the information provided by the device manufacturer.

The manufacturer's instructions for using the pen must be carefully followed for loading the cartridge, attaching the needle, and administering the insulin injection.

Before inserting the cartridge into the reusable pen, the cartridge should be stored at room temperature for 1 to 2 hours.

Inspect the cartridge before use. Only use if the solution is clear, colorless, and free of visible particles.

Do not shake or mix before use.

After inserting a new cartridge:

You must check that your insulin pen is working properly before injecting your first dose (see the instructions for use of your pen).

Special precautions before injection

Air bubbles must be removed from the cartridge before injection (see pen instructions for use). Empty cartridges must not be refilled.

To prevent contamination, the reusable pen must be used only by you.

Problems with the insulin pen?

Please refer to the manufacturer's instructions for use of the pen.

If your insulin pen is damaged or not working properly (due to mechanical problems), it must be discarded and a new insulin pen used.

If you use more Apidra than you should

• If you have injected too much Apidra, your blood sugar level may become very low (hypoglycemia). Check your blood sugar level frequently. In general, to prevent hypoglycemia, you should eat more and monitor your blood sugar level. For more information on the treatment of hypoglycemia, see the box at the end of this leaflet.

If you forget to use Apidra

• If you have forgotten a dose of Apidra or if you have not injected enough insulin, your blood sugar level may become very high (hyperglycemia). Check your blood sugar level frequently. For more information on the treatment of hyperglycemia, see the box at the end of this leaflet.
• Do not use a double dose to make up for a missed dose.

If you stop using Apidra

This could lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (increased acid in the blood due to breakdown of fats instead of sugar). Do not stop using Apidra without consulting your doctor; he or she will advise you on what to do.

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

Insulin mix-ups

Always check the insulin label before each injection to avoid confusion between Apidra and other insulins.

4. Possible side effects

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

Serious side effects

Hypoglycaemia (low blood sugar levels) can be very serious. Hypoglycaemia is a very common side effect (may affect more than 1 in 10 people).

Hypoglycaemia (low blood sugar levels) means that you do not have enough sugar in your blood. If your blood sugar level drops too low, you may lose consciousness. Severe hypoglycaemia can cause brain damage and may be life-threatening. If you experience symptoms of low blood sugar, act immediately to raise your blood sugar level. See the box at the end of this leaflet for important information about hypoglycaemia and its treatment.

If you experience the following symptoms, contact your doctor immediately:

Systemic allergic reactions are uncommon side effects (may affect up to 1 in 100 people).

Generalised allergy to insulin: related symptoms may include widespread skin reactions (rash and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), difficulty breathing, drop in blood pressure with rapid heartbeat and sweating. These may be symptoms of severe generalised allergic reactions to insulin, including anaphylactic reaction, which may be life-threatening.

Hyperglycaemia (high blood sugar levels) means that there is too much sugar in the blood.

The frequency of hyperglycaemia cannot be estimated. If your blood sugar level is too high, this may indicate that you need more insulin than the amount you have injected. This can become serious if your blood sugar level becomes very high.

For more information on the signs and symptoms of hyperglycaemia, see the box at the end of this leaflet.

Other side effects

• Skin changes at the injection site.

If you inject insulin too frequently in the same place, fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy) (may affect up to 1 in 1,000 people). Lumps under the skin may also occur due to the build-up of a protein called amyloid (cutaneous amyloidosis; frequency unknown). Insulin may not work as well if injected into a lumpy area. Change your injection site to help prevent these skin changes.

Common side effects (may affect up to 1 in 10 people)

• Allergic and skin reactions at the injection site

Reactions at the injection site (such as redness, unusually severe pain during injection, itching, hives, swelling or inflammation) may occur. These reactions may also spread around the injection site. Most minor reactions to insulin usually resolve within a few days or weeks.

Side effects whose frequency cannot be estimated from available data

Eye reactions

A significant change (improvement or worsening) in your blood sugar control may temporarily worsen your vision. If you have proliferative retinopathy (a diabetes-related eye disease), severe hypoglycaemic attacks may cause temporary loss of vision.

Reporting of side effects

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

5. Storage of Apidra

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

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

Unopened cartridges

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Do not place Apidra near the freezer compartment or next to a cooling element. Keep the cartridge in its outer packaging to protect it from light.

Cartridges in use

Cartridges in use (in the insulin pen) may be kept for up to 4 weeks at below 25°C, protected from direct heat and direct light, and must not be stored in the refrigerator. Do not use after this period.

Do not use this medicine if it is not colourless and clear.

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

6. Contents of the container and other information

Composition of Apidra

• The active substance is insulin glulisine. Each millilitre of solution contains 100 Units of insulin glulisine (equivalent to 3.49 mg). Each cartridge contains 3 ml of injectable solution, equivalent to 300 Units.
• The other components are: metacresol (see section 2 “Apidra contains metacresol”), sodium chloride (see section 2 “Important information about some of the components of Apidra”), trometamol, polysorbate 20, concentrated hydrochloric acid, sodium hydroxide, water for injections.

Appearance of the product and contents of the container

Apidra 100 Units/ml solution for injection in cartridge is a clear, colourless aqueous solution free from visible particles.

Each cartridge contains 3 ml of solution (300 U). Pack sizes of 1, 3, 4, 5, 6, 8, 9 and 10 cartridges of 3 ml are available. Only some pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany

Manufacturer:

Sanofi-Aventis Deutschland GmbH
Industriepark Höchst, D-65926 Frankfurt
Germany

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

Belgium/Belgium/Belgium Sanofi Belgium Tel/Tel: +32 (0)2 710 54 00	Luxembourg/Luxembourg Sanofi Belgium Tel/Tel: +32 (0)2 710 54 00 (Belgium/Belgium)
	Hungary SANOFI-AVENTIS Zrt. Tel.: +36 1 505 0050
Czech Republic Sanofi s.r.o. Tel: +420 233 086 111	Malta Sanofi S.r.l. Tel: +39 02 39394275
Denmark Sanofi A/S Tlf: +45 45 16 70 00	Netherlands Sanofi B.V. Tel: +31 20 245 4000
Germany Sanofi-Aventis Deutschland GmbH Tel.: 0800 52 52 010 Tel. from abroad: +49 69 305 21 131	Norway sanofi-aventis Norge AS Tlf: +47 67 10 71 00
Estonia Swixx Biopharma OÜ Tel: +372 640 10 30	Austria sanofi-aventis GmbH Tel: +43 1 80 185 – 0
Greece Sanofi-Aventis Μονοπρόσωπη AEBE Tel: +30 210 900 16 00	Poland Sanofi Sp. z o.o. Tel.: +48 22 280 00 00
Spain sanofi-aventis, S.A. Tel: +34 93 485 94 00	Portugal Sanofi - Produtos Farmacêuticos, Lda. Tel: +351 21 35 89 400
France Sanofi Winthrop Industrie Tél: 0 800 222 555 Call from abroad: +33 1 57 63 23 23	Romania Sanofi Romania SRL Tel: +40 (0) 21 317 31 36
Croatia Swixx Biopharma d.o.o. Tel: +385 1 2078 500 Ireland sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +353 (0) 1 403 56 00	Slovenia Swixx Biopharma d.o.o. Tel: +386 1 235 51 00
Iceland Vistor hf. Sími: +354 535 7000	Slovakia Swixx Biopharma s.r.o. Tel: +421 2 208 33 600
Italy Sanofi S.r.l. Tel: 800 13 12 12 (technical inquiries) 800 536389 (other inquiries)	Finland Sanofi Oy Puh/Tel: +358 (0) 201 200 300
Cyprus C.A. Papaellinas Ltd. Tel: +357 22 741741	Sweden Sanofi AB Tel: +46 (0)8 634 50 00
Latvia Swixx Biopharma SIA Tel: +371 6 616 47 50	United Kingdom (Northern Ireland) sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +44 (0) 800 035 2525
Lithuania Swixx Biopharma UAB Tel: +370 5 236 91 40

Date of latest review of this leaflet:

Another source of information

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

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar with you (at least 20 grams).

Carry some identification indicating that you are a person with diabetes.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar level is very high (hyperglycaemia), it may be because you have not injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

• you have not injected your insulin, or have not injected a sufficient amount, or its effect has decreased, for example due to incorrect storage,
• you are doing less physical activity than usual, are under stress (emotional distress, excitement), or have an injury, surgery, infection, or fever,
• you are taking or have taken certain medicines (see section 2, “Use of Apidra with other medicines”).

Warning signs of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, flushed face, loss of appetite, low blood pressure, rapid heartbeat, and presence of glucose and ketone bodies in the urine. Stomach pain, deep and rapid breathing, drowsiness, or even loss of consciousness may be signs of a serious condition (ketoacidosis) due to lack of insulin.

What to do in case of hyperglycaemia?

You must check your blood sugar level and your urine ketone level as soon as any of the symptoms described above occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, usually in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level drops too low, you may lose consciousness. Severe hypoglycaemia can lead to heart attack or brain damage and may be life-threatening. You should normally be able to recognize when your blood sugar level is dropping too low so that you can take appropriate action.

Why does hypoglycaemia occur?

Examples include:

• you inject too much insulin,
• you miss or delay meals,
• you do not eat enough, or eat foods containing fewer carbohydrates than usual (sugars and sugar-like substances are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),
• you lose carbohydrates due to vomiting or diarrhoea,
• you drink alcohol, especially if you are not eating much,
• you do more physical activity than usual or a different type of physical activity,
• you are recovering from an injury, surgery, or other types of stress,
• you are recovering from an illness or fever,
• you are taking or have stopped taking certain medicines (see section 2, “Use of Apidra with other medicines”).

Hypoglycaemia is also more likely if:

• you have recently started insulin treatment or have switched to another insulin preparation,
• your blood sugar levels are nearly normal or unstable,
• you change the injection site on your skin (e.g. from the thigh to the upper arm),
• you have severe kidney or liver disease, or another illness such as hypothyroidism.

Warning signs of hypoglycaemia

• In your body

Examples of symptoms indicating that your blood sugar level is dropping too low or too quickly: sweating, moist and clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations, and irregular heartbeat. These symptoms often occur before symptoms of low sugar in the brain appear.

• In your brain

Examples of symptoms indicating low sugar in the brain: headache, intense hunger, nausea, vomiting, tiredness, drowsiness, sleep disturbances, restlessness, aggressive behaviour, difficulty concentrating, altered reactions, depression, confusion, speech disturbances (sometimes complete loss of speech), visual disturbances, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling around the mouth, dizziness, loss of self-control, inability to care for yourself, seizures, and loss of consciousness.

The early warning signs of hypoglycaemia (“warning symptoms”) may change, become milder, or be completely absent if:

• you are elderly,
• you have had diabetes for a long time,
• you suffer from a certain type of nerve disease (autonomic diabetic neuropathy),
• you have recently experienced an episode of hypoglycaemia (e.g. the day before) or if it develops gradually,
• you have nearly normal or at least much improved blood sugar levels,
• you are taking or have taken certain medicines (see section 2, “Use of Apidra with other medicines”).

In such cases, you may develop severe hypoglycaemia (or even faint) before realizing there is a problem. Always be aware of your warning symptoms. If necessary, more frequent blood sugar testing may help identify mild hypoglycaemic episodes that might otherwise go unnoticed. If you are unsure whether you can recognize your warning symptoms, avoid situations (such as driving a car) that could put you or others at risk due to hypoglycaemia.

What should you do if hypoglycaemia occurs?

1. Do not inject insulin. Immediately consume 10 to 20 g of sugar, such as glucose tablets, sugar lumps, or a sugary drink. Warning: artificial sweeteners and food products containing artificial sweeteners instead of sugar (such as diet drinks) are not helpful in treating hypoglycaemia.
2. Afterwards, eat something that has a long-acting effect on raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you.
3. If hypoglycaemia recurs, take another 10 to 20 g of sugar.
4. Consult a doctor immediately if you are unable to control the hypoglycaemia or if it recurs.

Inform your family, friends, and close contacts:

If you are unable to swallow or lose consciousness, you will need an injection of glucose or glucagon (a medicine that increases blood sugar levels). Such injections are justified even if you are not certain that hypoglycaemia is present.

It is advisable to check your blood sugar level immediately after glucose ingestion to confirm that you actually have hypoglycaemia.