Package Leaflet: Information for the User

Apidra100 Units/mL injectable solution in cartridge

Insulina glulisina

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have the same symptoms, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

2.What you need to know before using Apidra

3.How to use Apidra

4.Possible side effects

5.Storage of Apidra

6.Contents of the pack and additional information

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 above. Diabetes mellitus is a disease in which the body does not produce sufficient insulin to control blood sugar levels.

It is obtained through biotechnology. It has a rapid onset of action in 10-20 minutes and a short duration of action, approximately 4 hours.

No use Apidra

-If you are allergic to insulin glulisine or any of the other components of this medication (listed in section 6).

-If your blood sugar level is too low (hypoglycemia), follow the hypoglycemia guide (see the box at the end of this leaflet).

Warnings and precautions

Apidra in cartridges is only indicated for injection just under the skin with a reusable pen (see also section 3). Consult your doctor if you need to inject insulin by another method.

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

Follow closely the dosing instructions, monitoring (blood tests), diet, and physical activity (physical work and exercise) as instructed by your doctor.

Special patient groups

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

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

Changes in skin at the injection site.

The injection site should be rotated to avoid changes in the skin, such as lumps under the skin. Insulin may not work well if injected in a swollen area (see How to use Apidra). Contact your doctor if you are currently injecting in a swollen area, before starting to inject in a different area. Your doctor may instruct you to check your blood sugar levels more closely, and adjust the insulin or the dose of your other diabetes medications.

Travel

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

-The availability of your insulin in the country you are traveling to,

-Insulin reserves, needles, etc.,

-The correct storage of insulin during the trip,

-The meal and insulin administration schedule during the trip,

-The possible effects of traveling to areas with time zone differences,

-The possible new health risks in the countries you will visit,

-What to do in emergency situations when you are ill or become sick.

Illnesses and injuries

The management of your diabetes may require special care in the following situations:

-If you are ill or have a major injury, your blood sugar level may increase (hyperglycemia).

-If you do not eat enough, your blood sugar level may drop too low (hypoglycemia). In most cases, you will need to see a doctor.Make sure to consult a doctor immediately.

If you have type 1 diabetes (insulin-dependent diabetes), do not stop administering your insulin and do not stop taking enough carbohydrates. Always inform the people taking care of you or treating you that you need insulin.

Some patients with long-term type 2 diabetes and previous heart disease or stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience symptoms of heart failure such as shortness of breath or rapid weight gain or localized swelling (edema).

Using Apidra with other medications

Some medications can change your blood sugar levels (increase, decrease, or both depending on the situation). In each case, you may need to adjust your insulin dose to avoid both low and high blood sugar levels. Be careful when starting another medication and also when stopping it.

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication. Ask your doctor before taking a medication if it can affect your blood sugar level, and what measures you should take.

Among the medications that can cause a decrease in your blood sugar level (hypoglycemia) are:

• All other diabetes medications,
• Inhibitors of the angiotensin-converting enzyme (ACE) (used to treat certain heart or hypertension diseases),
• Disopyramide (used to treat certain heart diseases),
• Fluoxetine (used to treat depression),
• Fibrates (used to reduce elevated blood lipid levels),
• Inhibitors of monoamine oxidase (MAO) (used to treat depression),
• Pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and reduce fever),
• Sulfonamide antibiotics.

Among the medications that can cause an increase in your blood sugar level (hyperglycemia) are:

• Corticosteroids (such as "cortisone" used to treat inflammation),
• Danazol (a medication that acts on ovulation),
• Diazoxide (used to treat hypertension),
• Diuretics (used to treat hypertension or excess fluid retention),
• Glucagon (pancreatic hormone used to treat severe hypoglycemia),
• Isoniazid (used to treat tuberculosis),

• Estrogens and progestogens (such as birth control pills used for birth control),

• Derivatives of phenothiazine (used to treat psychiatric disorders),
• Somatotropin (growth hormone),

• Medications that mimic the sympathetic nervous system (such as epinephrine [adrenaline], salbutamol, terbutaline, used to treat asthma),

• Thyroid hormones (used to treat thyroid gland disorders),
• Inhibitors of protease (used to treat HIV),
• Atypical antipsychotic medications (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 some parasitic infections) can cause hypoglycemia, which sometimes may be followed by hyperglycemia.

Beta-blockers, like other sympathetic nervous system inhibitors (such as clonidine, guanethidine, and reserpine), can attenuate or suppress the early warning symptoms that may help you recognize hypoglycemia.

If you are unsure whether you are taking any of these medications, 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, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

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

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

If you are breastfeeding, consult your doctor as you may need to adjust your insulin dose and diet.

Driving and operating machinery

Your ability to concentrate or react may be reduced if:

-You have hypoglycemia (low blood sugar levels),

-You have hyperglycemia (high blood sugar levels).

Be aware of this possible problem, considering all situations that may pose a risk to you or others (such as driving a vehicle or operating machinery).

You should ask your doctor for advice on driving if:

-You have frequent episodes of hypoglycemia,

-The early warning symptoms that may help you recognize hypoglycemia have decreased or do not appear.

Important information about some of the components of Apidra

This medication contains less than 1 mmol (23 mg) of sodium per dose, which is essentially "sodium-free".

Apidra contains metacresol

Apidra contains metacresol, which may cause allergic reactions.

Dosage

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

Your doctor will determine the dosage of Apidra you need based on your lifestyle and the results of your blood sugar (glucose) controls 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, long-acting insulin, a basal insulin, or oral medications used to treat high blood sugar levels.

If you switch from another insulin to glulisine insulin, your dosage may need to be adjusted by your doctor.

Many factors can affect your blood sugar levels. You should be aware of these factors so that you can react correctly to changes in your blood sugar levels and avoid them from rising or falling too much. See the box at the end of the prospectus for more information.

Administration Form

Apidra is injected under the skin (subcutaneously).

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

Administration Frequency

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

Instructions for Correct Use

How to handle cartridges

Apidra in cartridges is only indicated for injection just below the skin with a reusable pen. Consult your doctor if you need to inject insulin by another method.

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

• JuniorSTAR that releases doses in steps of 0.5 units
• ClikSTAR, Tactipen, Autopen 24, AllStar, or AllStar PRO that release doses in steps of 1 unit.

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

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

The manufacturer's instructions for using the pen should be followed carefully to load the cartridge, place the needle, and administer 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 it if the solution is transparent, colorless, and has no visible particles in it.

Do not shake or mix it before use.

After inserting a new cartridge:

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

Special Precautions Before Injection

Air bubbles must be removed from the cartridge before injection (see pen usage instructions). Empty cartridges should not be recharged.

To prevent any type of contamination, the reusable pen should only be used by you.

Problems with the Insulin Pen?

Please refer to the manufacturer's usage instructions for the pen.

If your insulin pen is damaged or does not work correctly (due to mechanical problems), it should be discarded and a new insulin pen used.

Using Too Much Apidra

- 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 control your blood sugar level. For more information on hypoglycemia treatment, see the box at the end of the prospectus.

Missing a Dose of Apidra

- If you have forgotten a dose of Apidra or if you have not injected enough insulin, your blood sugar level may increase greatly (hyperglycemia). Check your blood sugar level frequently. For more information on hyperglycemia treatment, see the box at the end of the prospectus.

- Do not use a double dose to compensate for missed doses.

Stopping Treatment with Apidra

This could produce severe hyperglycemia (very high blood sugar levels) and ketoacidosis (an increase in blood acid due to the body breaking down fats instead of sugar). Do not stop your treatment with Apidra without consulting your doctor, he will tell you what to do.

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

Confusion between Insulin

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

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

Severe side effects

Severe hypoglycemia (low blood sugar levels) can be very serious.Severe hypoglycemia is a frequently observed side effect(may affect more than 1 in 10 patients).

Severe hypoglycemia (low blood sugar levels) means you do not have enough sugar in your blood.If your blood sugar level drops too low, you may lose consciousness. Severe hypoglycemia can cause brain damage and be life-threatening. If you have symptoms of low blood sugar, actimmediatelyto raise your blood sugar level.See the box at the end of this leaflet, where you will find more important information about hypoglycemia and its treatment.

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

Thesystemic allergic reactionsare side effects that are infrequently observed (may affectup to 1 in 100 patients).

Generalized allergy to insulin:The symptoms associated with this may include widespread skin reactions (skin rash and itching all over the body), severe skin swelling or mucous membrane swelling (angioedema), difficulty breathing, low blood pressure with rapid heartbeat, and sweating.These may be symptoms of severe cases ofgeneralized allergy to insulin, including anaphylactic reaction that can be life-threatening.

Hypoglycemia (low blood sugar levels) means you do not have enough sugar in your blood.

The frequency of hypoglycemia cannot be estimated. If your blood sugar level is too high, this indicates that you may need more insulin than has been injected. This can be serious if your blood sugar level becomes very high.

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

Other side effects

• Changes in the skin at the injection site.

If insulin is injected too frequently in the same place, the fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy)(may affect up to 1 in 1,000 people). Bumps under the skin may also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis; it is not known how often this occurs). Insulin may not work well if injected in a swollen area. Change the injection site to help prevent these skin changes.

Frequent side effects(may affect up to 1 in 10 patients)

• Reactions to the skin and allergiesat the injection site

You may experience reactions at the injection site (such as redness, intense pain when injecting, itching, urticaria, swelling, or inflammation). These reactions may also spread around the injection site. Most minor reactions to insulin usually resolve on their own within a few days or weeks.

Side effects whose frequencycannot be estimated from the available data

• Eye reactions

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

Reporting side effects

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

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

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

Unopened cartridges

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

Do not freeze.

Do not place Apidra near the freezer compartment or next to a cold pack. Store the cartridge in the outer packaging to protect it from light.

In-use cartridges

In-use cartridges (in the insulin pen) may be stored for a maximum of 4 weeks below 25°C, protected from direct heat or direct light, and should not be stored in the refrigerator. Do not use after this period of time.

Do not use this medication if it is not colorless and transparent.

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

Composition of Apidra

-The other components are: metacresol (see section 2 “Apidra contains metacresol”), sodium chloride (see section 2 “Important information about some components of Apidra”), trometamol, polisorbate 20, concentrated hydrochloric acid, sodium hydroxide, water for injectable preparations.

Appearance of the product and contents of the pack

Apidra 100 Units/ml injectable solution in cartridge is a transparent, colorless, particle-free aqueous solution.

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

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

Responsible for manufacturing:

Sanofi-Aventis Deutschland GmbH

Industriepark Höchst, D-65926 Frankfurt

Germany

Further information on this medicinal product can be obtained by contacting the local representative of the holder of the marketing authorization.

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is availableon the website of the European Medicines Agency: http://www.ema.europa.eu/

It is recommended to analyse your blood sugar level immediately after ingesting glucose to confirm that you are actually experiencing hypoglycaemia.