PACKAGE LEAFLET: Information for the user

Apidra 100 Units/ml solution for injection in a vial

insulin glulisine
Please read all of this leaflet carefully before you start 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, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on 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, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

What Apidra is and what it is used for
What you need to know before using Apidra
How to use Apidra
Possible side effects
How to store Apidra
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 (glucose) levels in adult patients, adolescents, and children aged 6 years and older with diabetes mellitus. Diabetes mellitus is a condition in which the body does not produce enough insulin to control blood glucose levels.
Apidra is produced by means of a biotechnological process. It has a rapid onset of action within 10–20 minutes and a short duration of action of approximately 4 hours.

2. What you should 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 is too low (hypoglycaemia), follow the guidelines for hypoglycaemia (see the box at the end of this leaflet).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Apidra.
Carefully follow the instructions regarding dosage, monitoring (blood tests), diet, and physical activity (work and exercise) discussed with 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:
You must rotate your injection sites 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 Apidra"). 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 may adjust your insulin dose or that of other antidiabetic medicines.

Travel
Before travelling, consult your doctor. You may need to discuss the following:

Availability of insulin in your destination country,
Sufficient supplies of insulin, syringes, etc.,
Proper storage of insulin during travel,
Timing between meals and insulin administration during travel,
Possible effects of time zone changes,
Risk of contracting new illnesses in the countries visited,
What to do in emergency situations if you feel unwell or become ill.

Illness and injury
In the following situations, diabetes control may require closer attention:

If you are ill or have serious injuries, there is a risk that your blood sugar level may rise (hyperglycaemia).
If you do not eat enough, there is a risk that your blood sugar level may drop (hypoglycaemia). In most cases, medical intervention is necessary. Contact your doctor promptly.

Additionally, if you have type 1 diabetes (insulin-dependent diabetes mellitus), do not stop your insulin treatment or stop consuming carbohydrates. You should also ensure that people close to you are aware of your need for insulin.
Some patients with long-standing type 2 diabetes mellitus and heart disease or a history of stroke, 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 unusually short breath, rapid weight gain, or localized swelling (oedema).

Other medicines and Apidra
Some medicines can cause changes in blood sugar levels (either lowering or raising them, or both, depending on the situation). In any case, insulin dosage may need to be adjusted to avoid blood sugar levels that are too low or too high. Be cautious when starting or stopping any other medication.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Before taking any medicine, ask your doctor whether, and how, it may affect your blood sugar levels and whether you need to take any precautions.

Medicines that can cause a decrease in blood sugar levels (hypoglycaemia) include:

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

Medicines that can cause an increase in blood sugar levels (hyperglycaemia) include:

corticosteroids (such as "cortisone", used to treat inflammation),
danazol (a drug affecting ovulation),
diazoxide (used to treat high blood pressure),
diuretics (used to treat high blood pressure or excessive fluid retention),
glucagon (a pancreatic hormone used to treat severe hypoglycaemia),
isoniazid (used to treat tuberculosis),
oestrogens and progestogens (such as in oral contraceptives used for birth control),
phenothiazine derivatives (used to treat psychiatric disorders),
somatropin (growth hormone),
sympathomimetic agents (such as epinephrine [adrenaline], salbutamol, terbutaline, used to treat asthma),
thyroid hormones (used to treat thyroid disorders),
protease inhibitors (used to treat HIV),
atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

beta-blockers (used to treat high blood pressure),
clonidine (used to treat high blood pressure),
lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat certain parasitic infections) may cause hypoglycaemia, sometimes followed by hyperglycaemia.
Beta-blockers, as well as all other sympatholytic agents (such as clonidine, guanethidine, and reserpine), may reduce or completely mask the warning signs that help you recognize hypoglycaemia.
If you are unsure whether you are taking any of these medicines, ask your doctor or pharmacist.

Apidra with alcohol
Your blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Inform your doctor if you are planning a pregnancy or are already pregnant. You may need to adjust your insulin dose during pregnancy and after delivery. It is important to carefully control your diabetes and prevent hypoglycaemia for the health of your baby.
There are no data or limited data on the use of Apidra in pregnant women.
If you are breastfeeding, consult your doctor, as adjustments to your insulin dose and diet may be necessary.

Driving and using machines
Your ability to concentrate or react may be reduced if you experience:

hypoglycaemia (low blood sugar levels)
hyperglycaemia (high blood sugar levels)

Take into account the possibility of this occurring in any situation where you could be at risk, as well as posing a risk to others (such as when driving a car or operating machinery). Consult your doctor for advice on whether it is appropriate for you to drive if:

you have frequent episodes of hypoglycaemia,
the typical warning signs helping you to identify hypoglycaemia are reduced or absent.

Important information on some ingredients of Apidra
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially sodium-free.
Apidra contains metacresol
Apidra contains metacresol, which may cause allergic reactions.

3. How to use Apidra

Dose
Use this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Based on your lifestyle, blood glucose test results, and previous insulin treatment, your doctor will determine the amount of Apidra you need.
Apidra is a short-acting insulin. Your doctor may recommend combining it with a long- or intermediate-acting insulin, a basal insulin, or 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 insulin dose.
Many factors can affect your blood sugar levels. It is important that you understand these factors so you can respond appropriately to changes in blood sugar levels and thereby avoid them becoming too high or too low. For further information, see the section at the end of this leaflet.

Method of administration
Apidra is injected under the skin (subcutaneously). It may also be administered intravenously by qualified healthcare professionals under close medical supervision.
Your doctor will indicate the most suitable injection site for Apidra. Apidra can be injected into the abdominal wall, thigh, or upper arm, or administered as a continuous infusion into the abdominal wall.
The effect of insulin will be slightly faster when injected into the abdominal wall.
As with all insulins, injection and infusion sites must be rotated with each injection within a chosen area (abdomen, thigh, or upper arm).

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

Instructions for correct use
How to use vials
Apidra vials are to be used with insulin syringes with the corresponding calibration scale and with an insulin pump infusion system.
Check the vial before use. Use only if the solution is clear, colourless, and free from visible particles. Do not shake or mix before use.
Always use a new vial if you notice that your blood sugar control has unexpectedly worsened. This is because the insulin may have lost some of its effectiveness. If you suspect a problem with Apidra, have it checked by your doctor or pharmacist.

If you need to mix two types of insulin
Apidra must not be mixed with any preparation except human NPH insulin.
If Apidra is mixed with human NPH insulin, Apidra must be drawn into the syringe first. The injection must be given immediately after mixing.

How to handle an insulin pump infusion system
Before using Apidra in a pump system, you should have received detailed instructions on how to use the pump system. In addition, you should have information on what to do in case of illness, blood sugar levels that are too high or too low, or pump malfunction.
Use the pump system recommended by your doctor. Read and follow the instructions provided with the insulin infusion pump. Follow your doctor’s instructions regarding basal infusion rate and bolus insulin doses to be taken at meals. Measure your blood glucose regularly to ensure you are benefiting from insulin infusion and to confirm that the insulin pump is working properly.
Replace the infusion set and reservoir at least every 48 hours using an aseptic technique. These instructions may differ from those provided with the insulin infusion pump. When using Apidra in a pump system, it is important to always follow these specific instructions. Failure to follow these specific instructions may lead to serious adverse events.
Apidra must never be mixed with diluents or any other insulin when used in a pump.

What to do in case of malfunction or incorrect use of the insulin pump infusion system
Problems with the pump or infusion set, or incorrect use of the pump, may result in inadequate insulin delivery. This can rapidly lead to hyperglycaemia and diabetic ketoacidosis (build-up of acid in the blood because the body is using fat instead of sugar). If your blood glucose starts to rise, consult your doctor, pharmacist, or nurse as soon as possible. They will advise you on what to do.
You may need to use Apidra with syringes or pens. You must always have an alternative system for subcutaneous insulin administration available in case of pump system failure.

If you use more Apidra than you should
If you have injected too high a dose of Apidra, your blood sugar levels may become too low (hypoglycaemia).
Check your blood sugar frequently. In general, to prevent hypoglycaemia, consume more substantial meals and monitor your blood sugar. For information on the treatment of hypoglycaemia, see the section at the end of this leaflet.

If you forget to use Apidra
If you have forgotten a dose of Apidra or did not inject enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see the section at the end of this leaflet. Do not take a double dose to make up for a forgotten dose.

If you stop using Apidra
This may lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood because the body is metabolizing fat instead of sugar). Do not stop using Apidra without consulting your doctor, who will advise you on what needs to be done.

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

Insulin interchangeability
You must always check the insulin label before each injection to avoid accidentally using the wrong medicine instead of Apidra.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Hypoglycaemia (low blood sugar levels) can be very serious. Hypoglycaemia is a very common adverse event (may affect more than 1 in 10 people).
Hypoglycaemia (low sugar levels) means that there is not enough sugar in the blood. If blood sugar levels drop too low, you may lose consciousness. Severe hypoglycaemic episodes can cause brain damage and may be life-threatening. If you experience symptoms of low blood sugar, act immediately to raise your blood sugar levels. See the box at the end of this leaflet for further important information about hypoglycaemia and how it should be treated.
If you have the following symptoms, contact your doctor immediately:
Systemic allergic reactions are adverse events reported uncommonly (may affect up to 1 in 100 people).
Generalised allergy to insulin: associated symptoms may include widespread skin reactions (rashes and itching over the entire body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating.
These could be symptoms of severe cases of a generalised allergic reaction to insulin, including an anaphylactic reaction, which could be life-threatening.
Hyperglycaemia means that there is too much sugar in the blood. The frequency of hyperglycaemia cannot be estimated. Very high blood sugar may indicate that more insulin may be needed than has been administered.
Hyperglycaemia can lead to diabetic ketoacidosis (build-up of acid in the blood because the body is using fat instead of sugar).
These are serious side effects.
These conditions can occur when there are problems with the infusion pump or when the pump system is used incorrectly.
This means that you might not always receive enough insulin to treat your diabetes.
If this happens, seek urgent medical assistance.
Always keep an alternative insulin delivery system available for subcutaneous injection (see section 3, “How to handle an infusion pump system” and “What to do if the infusion pump system malfunctions or is used incorrectly”).
For more information on signs and symptoms of hyperglycaemia, refer to the box at the end of this leaflet.
Other side effects

Skin changes at the injection site: If you inject insulin too often in the same spot, fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy) (may affect up to 1 in 1,000 people). Lumps under the skin may also be caused by the build-up of a protein called amyloid (cutaneous amyloidosis: frequency is unknown). 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.

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

Skin and allergic reactions at the injection site: Reactions may occur at the injection site (such as redness, unusually severe pain during injection, itching, wheals (blisters), swelling or inflammation). These disturbances may extend around the injection site. Most minor reactions to insulin resolve within a few days or weeks.

Side effects for which frequency cannot be estimated from the available data:

Ocular reactions: A marked change (improvement or worsening) in blood sugar levels can temporarily affect vision. If you have proliferative retinopathy (a diabetes-related eye disease), severe hypoglycaemic episodes can cause temporary loss of vision.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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.

5. How to store Apidra

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 carton and on the label of the
vial after Scad/Exp. The expiry date refers to the last day of that month.
Unopened vials
Store in a refrigerator (2°C–8°C).
Do not freeze.
Do not place Apidra in direct contact with the freezer compartment or with cooling packs.
Keep the vial in the outer packaging to protect the medicine from light.
Opened vials
After first use, the vial can be stored for up to 4 weeks in the original packaging at a temperature
below 25°C, away from direct heat or direct light. Do not use the vial after this period has elapsed.
It is recommended to record the date of first use on the vial label.
Do not use this medicine if the solution does not appear clear and colourless.
Do not dispose of any medicine 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 Apidra contains

The active substance is insulin glulisine. Each ml of solution contains 100 Units of insulin glulisine (equivalent to 3.49 mg). Each vial contains 10 ml of injectable solution, equivalent to 1000 Units.
The other components are: metacresol (see section 2 “Apidra contains”), sodium chloride (see section 2 “Important information on some components of Apidra”), tromethamine, polysorbate 20, concentrated hydrochloric acid, sodium hydroxide, water for injections.

Description of the appearance of Apidra and contents of the pack
Apidra 100 Units/ml solution for injection in a vial is an aqueous, clear, colourless solution free from visible particles.
Each vial contains 10 ml of solution (1000 Units). Packs containing 1, 2, 4 and 5 vials are available. Not all 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

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

België/Belgique/Belgien Lietuva
Sanofi Belgium UAB “SANOFI-AVENTIS LIETUVA”
Tél/Tel: +32 (0)2 710 54 00 Tel: +370 5 2755224
България Luxembourg/Luxemburg
Sanofi Bulgaria EOOD Sanofi Belgium
Тел.: +359 (0)2 970 53 00 Tél/Tel: +32 (0)2 710 54 00
(Belgique/Belgien)
Česká republika Magyarország
sanofi-aventis, s.r.o. SANOFI-AVENTIS Zrt., Tel.: +36 1 505
Tel: +420 233 086 111 0050
Danmark Malta
Sanofi A/S Sanofi S.r.l.
Tlf: +45 45 16 70 00 Tel: +39 02 39394275
Deutschland Nederland
Sanofi-Aventis Deutschland GmbH Genzyme Europe B.V.
Tel.: 0800 52 52 010 Tel: +31 20 245 4000
Tel. from abroad: +49 69 305 21 131
Eesti Norge
sanofi-aventis Estonia OÜ sanofi-aventis Norge AS
Tel: +372 627 34 88 Tlf: +47 67 10 71 00
Ελλάδα Österreich
sanofi-aventis AEBE sanofi-aventis GmbH
Τηλ: +30 210 900 16 00 Tel: +43 1 80 185 – 0
España Polska
sanofi-aventis, S.A. sanofi-aventis Sp. z o.o.
Tel: +34 93 485 94 00 Tel.: +48 22 280 00 00
France Portugal
sanofi-aventis France Sanofi - Produtos Farmacêuticos, Lda.
Tél: 0 800 222 555 Tel: +351 21 35 89 400
From abroad: +33 1 57 63 23 23
Hrvatska România
sanofi-aventis Croatia d.o.o. Sanofi Romania SRL
Tel: +385 1 600 34 00 Tel: +40 (0) 21 317 31 36
Ireland Slovenija
sanofi-aventis Ireland Ltd. T/A SANOFI sanofi-aventis d.o.o.
Tel: +353 (0) 1 403 56 00 Tel: +386 1 560 48 00
Ísland Slovenská republika
Vistor hf. sanofi-aventis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 33 100 100
Italia Suomi/Finland
Sanofi S.r.l. Sanofi Oy
Tel: 800 13 12 12 (technical enquiries) Puh/Tel: +358 (0) 201 200 300
800 536389 (other enquiries)
Sverige
Κύπρος Sanofi AB
sanofi-aventis Cyprus Ltd. Tel: +46 (0)8 634 50 00
Τηλ: +357 22 871600
Latvija United Kingdom
sanofi-aventis Latvia SIA Sanofi
Tel: +371 67 33 24 51 Tel: +44 (0) 845 372 7101

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

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar with you (at least 20 grams).
Carry identification indicating that you are a person with diabetes.

HYPERGLYCAEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?
Examples include:

you did not inject insulin, injected an insufficient amount, or the insulin has become less effective (e.g., due to improper storage),
you are doing less physical exercise than usual, or are under emotional or physical stress, or in case of injury, surgery, infection or fever,
you are taking or have taken certain other medicines (see section 2 “Apidra and other medicines”).

Warning symptoms of hyperglycaemia
Thirst, increased need to urinate, weakness, dry skin, flushed face, loss of appetite, low blood pressure, rapid heartbeat, and presence of glucose or ketone bodies in the urine. Abdominal pain, deep and rapid breathing, drowsiness or even loss of consciousness may indicate a serious condition (ketoacidosis) due to insulin deficiency.

What should you do in case of hyperglycaemia?
Check your blood sugar and test for the presence of ketone bodies in your urine as soon as possible if any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCAEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycaemic episodes can cause heart attack or brain damage and may be life-threatening.
Generally, you should be able to recognize when your blood sugar levels are dropping too low so that you can take appropriate precautions.

Why does hypoglycaemia occur?
Examples include:

you injected too much insulin,
you skipped or delayed meals,
you are not eating enough, or your food contains fewer carbohydrates than usual (carbohydrates are sugars and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
you have lost carbohydrates due to vomiting or diarrhoea,
you drink alcoholic beverages, especially if you are eating little,
you are doing more physical exercise than usual, or a different type of physical activity,
you are recovering from injury, surgery or stress,
you are recovering from illness or fever,
you are taking or have taken certain other medicines (see section 2 “Apidra and other medicines”).

Hypoglycaemia may also occur more easily if:

you have just started insulin treatment or have switched to a different type of insulin,
your blood sugar levels are close to normal or show fluctuations,
you have changed the skin area where you inject insulin (e.g., from the thigh to the upper arm),
you suffer from severe kidney or liver disease, or other conditions such as hypothyroidism.

Warning symptoms of hypoglycaemia

In the body Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, moist skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before those indicating reduced sugar levels in the brain.
In the brain Examples of symptoms indicating reduced sugar levels in the brain: headache, intense hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced reaction ability, depressed mood, confusion, speech difficulties (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paraesthesia), tingling and numbness sensations in the mouth, dizziness, loss of self-control, inability to care for oneself, seizures and loss of consciousness.

The characteristic early symptoms of hypoglycaemia (“warning symptoms”) may vary, be less evident or even completely absent if:

you are elderly,
you have had diabetes for a long time,
you suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
after a recent hypoglycaemic episode (e.g., the day before) or if hypoglycaemia develops slowly,
your blood glucose levels are nearly normal or significantly improved,
you are taking or have taken certain other medicines (see section 2 “Apidra and other medicines”).

In these cases, severe hypoglycaemia (even with loss of consciousness) may develop without timely recognition. Therefore, learn to recognize the warning symptoms. If necessary, more frequent blood glucose monitoring may help identify mild hypoglycaemic episodes that might otherwise go unnoticed. If you are unable to recognize the warning symptoms of hypoglycaemia, avoid situations (such as driving a car) that could be dangerous for you and others due to hypoglycaemia.

What should you do in case of hypoglycaemia?

Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes, or a sugary drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycaemia.
Then consume food that will cause a prolonged release of sugar into the blood (e.g., bread or pasta). Your doctor or nurse should have previously discussed these measures with you.
If another episode of hypoglycaemia occurs, take again 10 to 20 g of sugar.
Contact your doctor as soon as you notice that you are unable to control hypoglycaemia or if it recurs.

Inform your family, friends and close colleagues that:
if you are unable to swallow or lose consciousness, treatment with an injection of glucose or glucagon (a medicine that raises blood sugar levels) is required. These injections are justified even if it is not certain that a hypoglycaemic event has occurred.

It is advisable to check blood glucose immediately after taking sugar to confirm that a hypoglycaemic episode was occurring.

The following information is intended for healthcare professionals only:

Apidra can be administered intravenously. This must be done by qualified healthcare personnel.
Instructions for intravenous administration
Apidra must be used at a concentration of 1 Unit/ml of insulin glulisine in infusion systems with a sodium chloride 9 mg/ml (0.9%) solution for infusion, with or without 40 mmol/l of potassium chloride, using co-extruded polyolefin/polyamide plastic infusion bags with a dedicated infusion line. Insulin glulisine for intravenous use at a concentration of 1 Unit/ml is stable at room temperature for 48 hours.
After dilution for intravenous use, the solution should be inspected visually for the presence of suspended particles before administration. Only use if the solution is clear and colorless; do not use if it is cloudy or contains visible particles.
Apidra has been found to be incompatible with 5% glucose solution and Ringer's solution, and therefore must not be used with these solutions. The use of other solutions has not been studied.

PACKAGE LEAFLET: information for the user

Apidra 100 Units/ml injectable solution in a cartridge

insulin glulisine
Please read this leaflet carefully before using this medicine because it contains important information for you. Instructions for the use of the insulin pen are provided with your insulin pen. Refer to these before using your medicine.

Keep this leaflet. 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. 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, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Apidra is and what it is used for
What you need to know before using Apidra
How to use Apidra
Possible side effects
How to store Apidra
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 (glucose) levels in adult patients, adolescents, and children from the age of 6 years who have diabetes mellitus. Diabetes mellitus is a condition in which the body does not produce enough insulin to control blood glucose levels.
Apidra is produced by a biotechnological process. 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 is too low (hypoglycaemia), follow the guidelines for hypoglycaemia (see the box at the end of this leaflet).

Warnings and precautions
Apidra in cartridges is intended solely for subcutaneous injection with a reusable pen (see section 3). Speak with your doctor if you need to administer insulin by another method.
Talk to your doctor, pharmacist, or nurse before using Apidra.
Carefully follow the instructions regarding dosage, monitoring (blood tests), diet, and physical activity (work and exercise) discussed with your treating physician.

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 Apidra"). If you currently inject 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 medicines.

Travel
Before traveling, consult your doctor. You may need to discuss the following:

Availability of insulin in your destination country,
Adequate supply of insulin, needles, etc.,
Proper storage of insulin during travel,
Timing between meals and insulin administration during travel,
Possible effects of time zone changes,
Risk of contracting new illnesses in the countries visited,
What to do in emergency situations if you feel unwell or become ill.

Illness and injury
In the following situations, diabetes control may require closer attention:

If you are ill or have serious injuries, there is a risk that your blood sugar level may rise (hyperglycaemia).
If you do not eat enough, there is a risk that your blood sugar level may drop (hypoglycaemia). In most cases, medical intervention is necessary. Contact your doctor promptly.

Additionally, if you have type 1 diabetes (insulin-dependent diabetes mellitus), do not stop insulin treatment or carbohydrate intake. It is also important to inform people close to you about your need for insulin.
Some patients with long-standing type 2 diabetes mellitus and heart disease or a history of stroke, 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 unusually shortness of breath, rapid weight gain, or localized swelling (oedema).

Other medicines and Apidra
Some medicines can cause changes in blood sugar levels (either lowering or raising them, or both, depending on the situation). In any case, insulin dosage may need to be adjusted to avoid blood sugar levels that are too low or too high. Be cautious when starting or stopping any other medication.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Before taking any medicine, ask your doctor whether, and how, it may affect your blood sugar levels and whether you need to take any precautions.

Medicines that may cause a decrease in blood sugar levels (hypoglycaemia) include:

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

Medicines that may cause an increase in blood sugar levels (hyperglycaemia) include:

corticosteroids (such as "cortisone", used to treat inflammation),
danazol (a drug that affects ovulation),
diazoxide (used to treat high blood pressure),
diuretics (used to treat high blood pressure or excessive fluid retention),
glucagon (a pancreatic hormone used to treat severe hypoglycaemia),
isoniazid (used to treat tuberculosis),
oestrogens and progesterone (as in oral contraceptives used for birth control),
phenothiazine derivatives (used to treat psychiatric disorders),
somatropin (growth hormone),
sympathomimetic agents (such as epinephrine [adrenaline], salbutamol, terbutaline, used to treat asthma),
thyroid hormones (used to treat thyroid disorders),
protease inhibitors (used to treat HIV),
atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

beta-blockers (used to treat high blood pressure),
clonidine (used to treat high blood pressure),
lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat certain parasitic infections) may cause hypoglycaemia, sometimes followed by hyperglycaemia.
Beta-blockers, as well as other sympatholytic agents (such as clonidine, guanethidine, and reserpine), may reduce or completely mask the warning signs that help you recognize hypoglycaemia.
If you are unsure whether you are taking any of these medicines, ask your doctor or pharmacist.

Apidra and alcohol
Your blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Inform your doctor if you are planning a pregnancy or are already pregnant. You may need to adjust your insulin dose during pregnancy and after delivery. It is important to carefully control your diabetes and prevent hypoglycaemia for the health of your baby.
There are no data or limited data on the use of Apidra in pregnant women.
If you are breastfeeding, consult your doctor, as adjustments to your insulin dose and diet may be necessary.

Driving and using machines
Your ability to concentrate or react may be reduced in case of

hypoglycaemia (low blood sugar levels),
hyperglycaemia (high blood sugar levels).

Consider the possibility of this occurring in any situation where you might pose a risk to yourself or others (such as driving a car or operating machinery). Consult your doctor for advice on whether it is appropriate for you to drive if:

you have frequent hypoglycaemic episodes,
the typical warning signs that help you recognize hypoglycaemia are reduced or absent.

3. How to use Apidra

Dosage
Use this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Based on your lifestyle, blood glucose test results, and previous insulin use, your doctor will determine the amount of Apidra you need.
Apidra is a short-acting insulin. Your doctor may advise combining it with a long- or intermediate-acting insulin, a basal insulin, or oral antidiabetic tablets used to treat high blood sugar levels.
If you switch from another insulin to insulin glulisine, your doctor may need to adjust your insulin dose.
Many factors can affect your blood sugar levels. It is important that you understand these factors so you can respond appropriately to changes in blood glucose, thereby avoiding levels that are too high or too low. For further information, see the box at the end of this leaflet.

Method of administration
Apidra is injected under the skin (subcutaneously).
Your doctor will indicate the most suitable injection site for Apidra. Apidra can be injected into the abdominal wall, thigh, or upper arm, or administered as a continuous infusion into the abdominal wall.
The effect of insulin may be slightly faster when injected into the abdominal wall.
As with all insulins, injection and infusion sites should be rotated with each injection within a chosen area (abdomen, thigh, or upper arm).

Frequency of administration
Apidra should be administered just before or immediately after meals (0–15 minutes).

Instructions for proper use

How to use the cartridges
Apidra in cartridges is intended only for subcutaneous injection using a reusable insulin pen. Please consult your
physician if you need to administer insulin by any other method.
Apidra cartridges must be used only with the following pens:

JuniorStar, for administering Apidra in dose increments of 0.5 units
ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO, for administering Apidra in dose increments of 1 unit.
These cartridges must not be used with any other reusable pen, as dosing accuracy has been established only with the pens listed above. Not all of these pens may be available in your country.

The pens must be used according to the recommendations provided by the device manufacturer.
Carefully follow the manufacturer's instructions for using the pen, including cartridge loading, needle insertion, and insulin administration.
It is recommended to store the cartridge at room temperature for 1–2 hours before inserting it into the pen.
Inspect the cartridge before use. Use only if the solution is clear, colourless, and free of visible particles.
Do not shake or mix before use.

Special precautions before injection
Before use, remove all air bubbles (refer to the pen user instructions).
Do not refill empty cartridges.
To prevent contamination, the pen must be used only by you and not shared with others.

Problems with the insulin pen?
Refer to the manufacturer's instructions for pen use.
If the insulin pen is damaged or not functioning properly (due to mechanical defects), it must be discarded and a new insulin pen used.

If you use more Apidra than you should
If you have injected too high a dose of Apidra, your blood sugar levels may become too low (hypoglycaemia).
Check your blood sugar frequently. In general, to prevent hypoglycaemia, consume more substantial meals and monitor your blood sugar levels. For information on treating hypoglycaemia, see the box at the end of this leaflet.

If you forget to use Apidra
If you have forgotten a dose of Apidra or have not injected enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on treating hyperglycaemia, see the box at the end of this leaflet.
Do not take a double dose to make up for a missed dose.

If you stop using Apidra
This may lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood due to the body metabolizing fat instead of sugar). Do not stop using Apidra without consulting your doctor, who will advise you on what steps to take.

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

Switching insulins
You must always check the insulin label before each injection to avoid accidentally confusing Apidra with other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Hypoglycaemia (low blood sugar levels) can be very serious. Hypoglycaemia is a very commonly reported adverse event (may affect more than 1 in 10 people). Hypoglycaemia (low blood sugar) means that there is not enough sugar in the blood. If blood sugar levels drop too low, you may lose consciousness. Severe hypoglycaemic episodes can cause brain damage and may be life-threatening. If you experience symptoms of low blood sugar, act immediately to raise your blood sugar levels. See the box at the end of this leaflet for further important information on hypoglycaemia and how it should be treated.
If you have the following symptoms, contact your doctor immediately:
Systemic allergic reactions are adverse events reported uncommonly (may affect up to 1 in 100 people).
Generalised allergy to insulin: associated symptoms may include widespread skin reactions (rashes and itching over the whole body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating. These could be symptoms of severe allergic reactions to insulin, including an anaphylactic reaction, which could be life-threatening.
Hyperglycaemia means that there is too much sugar in the blood. The frequency of hyperglycaemia cannot be estimated. High blood glucose may indicate that more insulin may be needed than has been administered. It can become serious if blood glucose becomes very high.
For more information on signs and symptoms of hyperglycaemia, refer to the box at the end of this leaflet.
Other side effects

Skin changes at the injection site: If you inject insulin too often in the same spot, the fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy) (may affect up to 1 in 1,000 people). Lumps under the skin may also be caused by the build-up of a protein called amyloid (cutaneous amyloidosis: frequency not known). 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.
Commonly reported side effects (may affect up to 1 in 10 people)
Skin and allergic reactions at the injection site: Reactions may occur at the injection site (such as redness, unusually intense pain during injection, itching, wheals (blisters), swelling or inflammation). These problems may spread around the injection site. Most minor reactions to insulin resolve within a few days or weeks.

Side effects whose frequency cannot be determined from available data:

Eye reactions: A marked change (improvement or worsening) in blood sugar levels may temporarily affect vision. If you have proliferative retinopathy (an eye disease associated with diabetes), severe hypoglycaemic episodes can cause temporary loss of vision.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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.

5. How to store Apidra

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the cartridge after Scad/Exp. The expiry date refers to the last day of that month.
Unopened cartridges
Store in a refrigerator (2°C–8°C).
Do not freeze.
Do not place Apidra in direct contact with the freezer compartment or with cooling packs.
Keep the cartridge in its outer packaging to protect the medicine from light.
Cartridges in use
Cartridges in use (in the insulin pen) may be stored for up to 4 weeks at a temperature below 25°C, away from direct heat or direct light. Do not store the cartridge in use in the refrigerator. Do not use after this period.
Do not use this medicine if the solution does not appear clear and colourless.
Do not dispose of medicines 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 Apidra Contains

The active substance is insulin glulisine. Each ml 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”), sodium chloride (see section 2 “Important information on some components of Apidra”), trometamol, polysorbate 20, concentrated hydrochloric acid, sodium hydroxide, water for injections.

Description of the Appearance of Apidra and Contents of the Pack
Apidra 100 Units/ml solution for injection in a cartridge is a clear, colourless aqueous solution without visible particles.
Each cartridge contains 3 ml of solution (300 Units). Packs containing 1, 3, 4, 5, 6, 8, 9 and 10 cartridges are available. Not all 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

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

België/Belgique/Belgien Lietuva
Sanofi Belgium UAB “SANOFI-AVENTIS LIETUVA”
Tél/Tel: +32 (0)2 710 54 00 Tel: +370 5 2755224

България Luxembourg/Luxemburg
Sanofi Bulgaria EOOD Sanofi Belgium
Тел.: +359 (0)2 970 53 00 Tél/Tel: +32 (0)2 710 54 00
(Belgique/Belgien)

Česká republika Magyarország
sanofi-aventis, s.r.o. SANOFI-AVENTIS Zrt.,
Tel: +420 233 086 111 Tel.: +36 1 505 0050

Danmark Malta
Sanofi A/S Sanofi S.r.l.
Tlf: +45 45 16 70 00 Tel: +39 02 39394275

Deutschland Nederland
Sanofi-Aventis Deutschland GmbH Genzyme Europe B.V.
Tel: 0800 52 52 010 Tel: +31 20 245 4000
Tel. from abroad: +49 69 305 21 131

Eesti Norge
sanofi-aventis Estonia OÜ sanofi-aventis Norge AS
Tel: +372 627 34 88 Tlf: +47 67 10 71 00

Ελλάδα Österreich
sanofi-aventis AEBE sanofi-aventis GmbH
Τηλ: +30 210 900 16 00 Tel: +43 1 80 185 – 0

España Polska
sanofi-aventis, S.A. sanofi-aventis Sp. z o.o.
Tel: +34 93 485 94 00 Tel.: +48 22 280 00 00

France Portugal
sanofi-aventis France Sanofi - Produtos Farmacêuticos, Lda.
Tél: 0 800 222 555 Tel: +351 21 35 89 400
From abroad: +33 1 57 63 23 23

Hrvatska România
sanofi-aventis Croatia d.o.o. Sanofi Romania SRL
Tel: +385 1 600 34 00 Tel: +40 (0) 21 317 31 36

Ireland Slovenija
sanofi-aventis Ireland Ltd. T/A SANOFI sanofi-aventis d.o.o.
Tel: +353 (0) 1 403 56 00 Tel: +386 1 560 48 00

Ísland Slovenská republika
Vistor hf. sanofi-aventis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 33 100 100

Italia Suomi/Finland
Sanofi S.r.l. Sanofi Oy
Tel: 800 13 12 12 (technical enquiries) Puh/Tel: +358 (0) 201 200 300
800 536389 (other enquiries)

Sverige
Κύπρος Sanofi AB
sanofi-aventis Cyprus Ltd. Tel: +46 (0)8 634 50 00
Τηλ: +357 22 871600

Latvija United Kingdom
sanofi-aventis Latvia SIA Sanofi
Tel: +371 67 33 24 51 Tel: +44 (0) 845 372 7101

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

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar with you (at least 20 grams).
Carry identification indicating that you have diabetes.

HYPERGLYCAEMIA (high blood sugar levels)
If your blood sugar levels are too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?
Examples include:

you have not injected insulin, or have injected too little, or the insulin has become less effective (e.g., due to improper storage),
you are doing less physical exercise than usual, or are under emotional or physical stress, or in case of injury, surgery, infection or fever,
you are taking or have taken certain other medicines (see section 2 “Apidra and other medicines”).

What should you do in case of hyperglycaemia?
Check your blood sugar and test for ketone bodies in your urine as soon as possible if any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, usually in a hospital setting.

HYPOGLYCAEMIA (low blood sugar levels)
If your blood sugar levels drop too low, you may lose consciousness. Severe hypoglycaemic episodes can cause heart attack or brain damage and may be life-threatening.
Generally, you should be able to recognise when your blood sugar levels are dropping too low, so that you can take appropriate precautions.

Why does hypoglycaemia occur?
Examples include:

you have injected too much insulin,
you have skipped or delayed meals,
you are not eating enough, or your food contains fewer carbohydrates than usual (carbohydrates are sugars and sugar-like substances; however, artificial sweeteners are NOT carbohydrates),
you have lost carbohydrates due to vomiting or diarrhoea,
you drink alcoholic beverages, especially if you are eating little,
you are doing more physical exercise than usual, or a different type of physical activity,
you are recovering from injury, surgery or stress,
you are recovering from illness or fever,
you are taking or have taken certain other medicines (see section 2 “Apidra and other medicines”).

Hypoglycaemia may also occur more easily if:

you have just started insulin treatment or have switched to a different type of insulin,
your blood sugar levels are close to normal or show fluctuations,
you have changed the area of skin where you inject insulin (e.g., from the thigh to the upper arm),
you suffer from severe kidney or liver disease, or other conditions such as hypothyroidism.

Warning symptoms of hypoglycaemia

In the body: Examples of symptoms indicating that blood sugar levels are dropping too low or too quickly: sweating, moist skin, anxiety, rapid heartbeat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before those indicating reduced brain sugar levels.
In the brain: Examples of symptoms indicating reduced brain sugar levels: headache, intense hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, reduced reaction ability, depressed mood, confusion, difficulty speaking (sometimes aphasia), visual disturbances, tremor, paralysis, sensory disturbances (paraesthesia), tingling and numbness around the mouth, dizziness, loss of self-control, inability to care for oneself, seizures and loss of consciousness.

The characteristic early symptoms of hypoglycaemia (“warning symptoms”) may vary, be less evident, or even completely absent if:

you are elderly,
you have had diabetes for a long time,
you suffer from a certain type of neurological disease (diabetic autonomic neuropathy),
you have recently experienced a hypoglycaemic episode (e.g., the day before) or if hypoglycaemia develops slowly,
your blood glucose levels are nearly normal or significantly improved,
you are taking or have taken certain other medicines (see section 2 “Apidra and other medicines”).

In these cases, severe hypoglycaemia (even with loss of consciousness) may develop without timely recognition. Therefore, learn to recognise your own warning symptoms. If necessary, more frequent blood glucose checks may help identify mild hypoglycaemic episodes that might otherwise go unnoticed. If you are unable to recognise the warning signs of hypoglycaemia, avoid situations (such as driving a car) that could be dangerous for you and others due to hypoglycaemia.

What should you do in case of hypoglycaemia?

Do not inject insulin. Immediately take 10 to 20 g of sugar, such as glucose, sugar cubes or a sugary drink. Caution: artificial sweeteners and foods containing artificial sweeteners (such as diet drinks) do not help treat hypoglycaemia.
Then eat food that will cause a prolonged release of sugar into the blood (e.g., bread or pasta). Your doctor or nurse should discuss these measures with you in advance.
If another episode of hypoglycaemia occurs, take another 10 to 20 g of sugar.
Contact your doctor as soon as you realise you cannot control the hypoglycaemia or if it recurs.

Inform your close family members, friends and colleagues that:
if you are unable to swallow or lose consciousness, treatment with an injection of glucose or glucagon (a medicine that raises blood sugar levels) is required. Such injections are justified even if it is not certain that a hypoglycaemic event has occurred.
It is advisable to check blood glucose immediately after taking sugar to confirm that a hypoglycaemic episode was occurring.

INSTRUCTIONS FOR USE: information for the user

Apidra SoloStar 100 Units/ml solution for injection in a pre-filled pen

insulin glulisine
Please read this leaflet carefully, including the Instructions for Use of Apidra SoloStar pre-filled pen, 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, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Apidra is and what it is used for
What you need to know before using Apidra
How to use Apidra
Possible side effects
How to store Apidra
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 (glucose) levels in adult, adolescent patients and children from the age of 6 years with diabetes mellitus. Diabetes mellitus is a condition in which the body does not produce enough insulin to control blood glucose levels.
Apidra is produced by a biotechnological process. It has a rapid onset of action within 10–20 minutes and a short duration of action of approximately 4 hours.

2. What you should 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 is too low (hypoglycaemia), follow the guidelines for hypoglycaemia (see the box at the end of this leaflet).

Warnings and precautions
Apidra in the pre-filled pen is intended only for subcutaneous injections (also see section 3).
Talk to your doctor if you need to inject insulin by another method.
Consult your doctor, pharmacist, or nurse before using Apidra.
Carefully follow the instructions regarding dosage, monitoring (blood tests), diet, and physical activity (work and exercise) discussed with your treating doctor.

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 Apidra"). If you currently inject into an area with lumps, consult your doctor before switching to another injection site. Your doctor may advise you to monitor your blood sugar more closely and possibly adjust your insulin dose or that of other antidiabetic medicines.

Travelling
Before travelling, consult your doctor. You may need to discuss the following:

Availability of insulin in the destination country,
Adequate supplies of insulin, needles, etc.,
Proper storage of insulin during travel,
Timing of meals and insulin administration during travel,
Possible effects of time zone changes,
Risk of contracting new illnesses in the countries visited,
What to do in emergency situations if you feel unwell or become ill.

Illness and injury
In the following situations, diabetes control may require closer attention:

If you are ill or have serious injuries, there is a risk that your blood sugar level may rise (hyperglycaemia).
If you do not eat enough, there is a risk that your blood sugar level may drop (hypoglycaemia). In most cases, medical intervention is required. Contact your doctor promptly.

Additionally, if you have type 1 diabetes (insulin-dependent diabetes mellitus), do not stop insulin treatment or carbohydrate intake. Inform people close to you about your need for insulin.
Some patients with long-standing type 2 diabetes mellitus and heart disease or a history of stroke, 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 unusually short breath, rapid weight gain, or localized swelling (oedema).

Other medicines and Apidra
Some medicines may cause changes in blood sugar levels (either lowering or raising, or both, depending on the situation). In any case, insulin dosage may need to be optimised to avoid blood sugar levels that are too low or too high. Be cautious when starting or stopping any other medication.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Before taking any medicine, ask your doctor whether, and how, it may affect your blood sugar and whether any preventive measures are needed.

Medicines that may cause a decrease in blood sugar levels (hypoglycaemia) include:

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

Medicines that may cause an increase in blood sugar levels (hyperglycaemia) include:

corticosteroids (such as "cortisone", used to treat inflammation),
danazol (a drug affecting ovulation),
diazoxide (used to treat high blood pressure),
diuretics (used to treat high blood pressure or excessive fluid retention),
glucagon (a pancreatic hormone used to treat severe hypoglycaemia),
isoniazid (used to treat tuberculosis),
estrogens and progesterone (as in oral contraceptives used for birth control),
phenothiazine derivatives (used to treat psychiatric disorders),
somatropin (growth hormone),
sympathomimetic agents (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),
thyroid hormones (used to treat thyroid disorders),
protease inhibitors (used to treat HIV),
atypical antipsychotic medicines (such as olanzapine and clozapine).

Blood sugar levels may decrease or increase if you take:

beta-blockers (used to treat high blood pressure),
clonidine (used to treat high blood pressure),
lithium salts (used to treat psychiatric disorders).

Apidra and alcohol
Your blood sugar levels may decrease or increase if you drink alcohol.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Inform your doctor if you are planning a pregnancy or are already pregnant. You may need to adjust your insulin dose during pregnancy and after delivery. It is important to carefully control your diabetes and prevent hypoglycaemia for the health of your baby.
There are no data or limited data on the use of Apidra in pregnant women.
If you are breastfeeding, consult your doctor, as adjustments to your insulin dose and diet may be necessary.

Driving and using machines
Your ability to concentrate or react may be reduced in case of

hypoglycaemia (low blood sugar levels),
hyperglycaemia (high blood sugar levels).

Take into account the possibility of this occurring in any situation where you may be putting yourself or others at risk (such as driving a car or operating machinery). Consult your doctor for advice on whether you should drive if:

you have frequent episodes of hypoglycaemia,
the typical warning signs helping you identify hypoglycaemia are reduced or absent.

Important information about some 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
Use this medicine exactly as instructed by your doctor. If in doubt, consult your doctor or pharmacist.
Based on your lifestyle, blood glucose test results, and previous insulin treatment, your doctor will determine the amount of Apidra you need.
Apidra is a short-acting insulin. Your doctor may recommend combining it with a long- or intermediate-acting insulin, a basal insulin, or oral 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 insulin dose.
Many factors can affect your blood sugar levels. It is important that you are aware of these factors so that you can respond appropriately to changes in blood glucose levels and thereby avoid them becoming too high or too low. For further information, see the section at the end of this leaflet.

Method of administration
Apidra is injected under the skin (subcutaneously).
Your doctor will indicate the most suitable injection site for Apidra. Apidra can be injected into the abdominal wall, thigh, or upper arm, or administered as a continuous infusion into the abdominal wall.
The effect of insulin will be slightly faster when injected into the abdominal wall.
As with all insulins, injection and infusion sites should be rotated from one injection to the next within a chosen area (abdomen, thigh, or upper arm).

Frequency of administration
Apidra should be administered just before or immediately after meals (0–15 minutes).

Instructions for Correct Use

How to use SoloStar
SoloStar is a disposable pre-filled pen containing insulin glulisine. Apidra in a pre-filled pen is intended only for subcutaneous injections. Please consult your doctor if you need to inject insulin by another method.
Read carefully the "Instructions for Use of SoloStar" included in this package leaflet.
You must use the pen exactly as described in these Instructions for Use.
To prevent possible transmission of diseases, each pen must be used by only one patient.
Before each use, always attach a new needle and perform the safety test. Use only needles that are compatible with SoloStar (see "Instructions for Use of SoloStar").
Check the cartridge inside the pen injector before use. Use it only if the solution is clear, colourless, and free of visible particles. Do not shake or mix before use.
Always start using a new pen if you notice that your blood sugar control has unexpectedly worsened. If you think you are having a problem with SoloStar, please consult your doctor or pharmacist.

If you use more Apidra than you should
If you have injected too high a dose of Apidra, your blood sugar levels may become too low (hypoglycaemia).
Check your blood sugar frequently. In general, to prevent hypoglycaemia, eat more substantial meals and monitor your blood sugar levels. For information on the treatment of hypoglycaemia, see the box at the end of this leaflet.

If you forget to use Apidra
If you have forgotten a dose of Apidra or did not inject enough insulin, your blood sugar levels may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see the box at the end of this leaflet.
Do not take a double dose to make up for a forgotten dose.

If you stop using Apidra
This may lead to severe hyperglycaemia (very high blood sugar levels) and ketoacidosis (build-up of acid in the blood due to the body metabolising fat instead of sugar). Do not stop using Apidra without consulting your doctor, who will advise you on what steps to take.

If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

Switching insulins
You must always check the insulin label before each injection to avoid accidentally using the wrong insulin, such as confusing Apidra with 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 commonly reported adverse event (may affect more than 1 in 10 people). Hypoglycaemia
(low blood sugar) means that there is not enough sugar in the blood. If blood sugar levels drop too low, you may lose consciousness. Severe hypoglycaemic episodes can cause brain damage and may be life-threatening. If you experience symptoms of low blood sugar, act immediately to raise your blood sugar levels. See the box at the end of this leaflet for further important information on hypoglycaemia and how it should be treated.
If you have the following symptoms, contact your doctor immediately:
Systemic allergic reactions are adverse events reported uncommonly (may affect up to 1 in 100 people).
Generalised allergy to insulin: symptoms may include widespread skin reactions (rashes and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), shortness of breath, low blood pressure with rapid heartbeat and sweating. These may be signs of severe cases of a generalised allergic reaction to insulin, including an anaphylactic reaction, which could be life-threatening.
Hyperglycaemia means that there is too much sugar in the blood. The frequency of hyperglycaemia cannot be estimated. High blood glucose may indicate that you may need more insulin than you have been given. It can be serious if blood glucose becomes very high.
For more information on signs and symptoms of hyperglycaemia, refer to the box at the end of this leaflet.
Other side effects

Skin changes at the injection site: If you inject insulin too often in the same spot, the fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy) (may affect up to 1 in 1,000 people). Lumps under the skin may also be caused by the build-up of a protein called amyloid (cutaneous amyloidosis: frequency cannot be estimated). 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.

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

Skin and allergic reactions at the injection site. Reactions may occur at the injection site (such as redness, unusually strong pain during injection, itching, wheals (blisters), swelling or inflammation). These problems may spread around the injection site. Most minor reactions to insulin resolve within a few days or weeks.

Side effects for which frequency cannot be estimated from the available data:

Eye reactions. A marked change (improvement or worsening) in blood sugar levels may temporarily affect vision. If you have proliferative retinopathy (a diabetes-related eye disease), severe hypoglycaemic episodes may cause temporary loss of vision.

5. How to store Apidra

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the pen after Scad/Exp. The expiry date refers to the last day of that month.
Pens not in use
Store in the refrigerator (2°C–8°C). Do not freeze. Do not place the SoloStar pen in direct contact with the freezer compartment or with cooling packs.
Keep the pre-filled pen in its outer packaging to protect the medicine from light.
Pens in use
Pens in use or kept as a "backup" may be stored for up to 4 weeks at a temperature below 25°C, away from direct heat or direct light, and must not be stored in the refrigerator.
Do not use the pen after this period.
Do not use this medicine if the solution is not clear and colourless.
Do not dispose of medicines 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 Apidra Contains

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

Description of the Appearance of Apidra and Contents of the Package
Apidra SoloStar 100 Units/ml injectable solution in a pre-filled pen. It is a clear, colourless, aqueous solution free from visible particles.
Each pen contains 3 ml of solution equivalent to 300 Units. Pack sizes of 1, 3, 4, 5, 6, 8, 9, and 10 pre-filled pens are available. Not all 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

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder.

België/Belgique/Belgien Lietuva
Sanofi Belgium UAB ”SANOFI-AVENTIS LIETUVA”
Tél/Tel: +32 (0)2 710 54 00 Tel: +370 5 2755224