INSUMAN BASAL 40 IU/ml INJECTABLE SUSPENSION IN A VIAL

Introduction

Package Leaflet: Information for the User

Insuman Basal 40 UI/ml injectable suspension in a vial

Human insulin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

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

1. What is Insuman Basal and what is it used for

Insuman Basal contains human insulin as the active substance, which is produced by a biotechnology process and is identical to the insulin produced by the human body.

Insuman Basal is an insulin preparation with a gradual onset of action and a long duration of action.

The insulin is present in the form of small crystals of protamine insulin.

Insuman Basal is used to reduce high blood sugar levels in patients with diabetes mellitus who require insulin treatment. Diabetes mellitus is a disease in which the body does not produce enough insulin to control blood sugar levels.

2. What you need to know before you use Insuman Basal

Do not use Insuman Basal

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

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

Follow strictly the instructions regarding dosage, monitoring (blood and urine tests), diet, and physical activity (work and exercise) as agreed with your doctor.

Consult your doctor if you are allergic to this medicine or to human insulins.

Special patient groups

If you have liver or kidney problems or if you are elderly, consult your doctor, as you may need a lower dose of insulin.

Changes in the 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 as well if it is injected into a lump (see How to use Insuman Basal). Contact your doctor if you are currently injecting into a lump, before starting to inject into a different area. Your doctor may advise you to check your blood sugar levels more closely and adjust your insulin or other anti-diabetic medications.

Travel

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

• the availability of insulin in the country you are traveling to,
• insulin, syringe, and other supplies,
• proper storage of insulin during travel,
• meal and insulin administration schedules during travel,
• possible effects of crossing time zones,
• 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 serious 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 a doctor. Make sure to consult a doctor immediately.

If you have type 1 diabetes (insulin-dependent diabetes mellitus), do not stop taking your insulin and follow a diet with sufficient carbohydrates. Always inform the people taking care of you that you need insulin.

Some patients with type 2 diabetes mellitus of long duration and previous 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 or rapid weight gain or localized swelling (edema).

Other medicines and Insuman Basal

Some medicines can change your blood sugar levels (either increasing or decreasing them, depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are too high or too low. Be careful when starting to take another medicine and also when stopping one.

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Ask your doctor before using a medicine if it can affect your blood sugar level and what measures you should take, if necessary.

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

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

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

• corticosteroids (such as "cortisone", used to treat inflammation),
• danazol (a medicine that affects ovulation),
• diazoxide (used to treat hypertension),
• diuretics (used to treat hypertension or excess fluid retention),
• glucagon (a pancreatic hormone used to treat severe hypoglycemia),
• isoniazid (used to treat tuberculosis),
• estrogens and progestogens (such as birth control pills used for contraception),
• phenothiazine derivatives (used to treat psychiatric diseases),
• somatotropin (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, olanzapine).

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

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

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

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

If you are not sure whether you are using any of these medicines, ask your doctor or pharmacist.

Insuman Basal with alcohol

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Tell your doctor if you are planning to have a baby or if you are already pregnant. Your insulin regimen may need to be changed during pregnancy and after delivery. Very careful control of your diabetes and prevention of hypoglycemia are important for the health of your baby. However, there is no experience with the use of Insuman Basal in pregnant women.

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

Driving and using machines

Your ability to concentrate or react may be reduced if

• you have hypoglycemia (low blood sugar levels)
• you have hyperglycemia (high blood sugar levels)
• you have vision problems.

Be aware of this possible problem, considering all situations that may pose a risk to you or others (such as driving a vehicle or using machines). You should ask your doctor for advice on your ability to drive if:

• you have frequent episodes of hypoglycemia,
• the early warning symptoms that could help you recognize hypoglycemia have decreased or disappeared.

Important information about some of the ingredients of Insuman Basal

This medicine contains less than 23 mg of sodium per dose; it is essentially "sodium-free".

3. How to use Insuman Basal

Dose

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. If you are not sure, consult your doctor or pharmacist again.

Based on your lifestyle and the results of your blood sugar (glucose) tests and your previous insulin treatment, your doctor will:

• determine the dose of Insuman Basal you need each day,
• tell you when to check your blood sugar level and if you need to perform urine tests,
• tell you when you may need to inject a higher or lower dose of Insuman Basal.

Many factors can influence your blood sugar level. You should know these factors so that you can react correctly to changes in your blood sugar level and avoid it becoming too high or too low. See the box at the end of this leaflet for more information.

Frequency of administration

Insuman Basal is injected under the skin 45 to 60 minutes before a meal.

Method of administration

Insuman Basal is a liquid (suspension) for injection under the skin.

Do not inject Insuman Basal into a vein (blood vessel).

Your doctor will show you which area of the skin to inject Insuman Basal into. With each injection, you should change the injection site within the area of skin you are using.

Do not use in insulin pumps or other infusion pumps. There are special insulin preparations for use in these devices.

How to handle the vials

Insuman Basal contains 40 UI of insulin per ml. Only syringes for injection designed for this concentration of insulin (40 UI per ml) should be used. The syringes for injection should not contain other medicines or residues of them (e.g., residues of heparin).

Before withdrawing the first dose of insulin, remove the removable protective cap from the vial.

Immediately before each injection, mix the insulin well. The best way to do this is to tilt the vial between the palms of your hands. Do not shake the vial vigorously, as this may cause foam to form. Foam can make it difficult to measure the correct dose.

After mixing, the suspension should have a uniform white, milky appearance. Do not use it if it remains transparent or if, for example, there are lumps, flakes, flocculation, or similar deposits in the suspension or on the walls or bottom of the vial. In such cases, use a new vial with a uniform suspension after mixing.

A new vial will also be used if you notice that your blood sugar control is unexpectedly worsening. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special precautions before injection

Before injection, remove all air bubbles. Make sure the insulin is not contaminated with alcohol or other disinfectants or with other substances. Do not mix insulin with any other medicine except for human insulin preparations as described below.

Insuman Basal can be mixed with all human insulin preparations, EXCEPT those designed specifically for insulin pumps. Similarly, it MUST NOT be mixed with insulins of animal origin or insulin analogs.

Your doctor will tell you if you need to mix human insulin preparations. If you need to inject a mixture, put Insuman Basal in the syringe first, before adding the other insulin. Inject immediately after mixing. Do not mix insulins of different concentrations (e.g., 100 UI/ml and 40 UI/ml).

If you use more Insuman Basal than you should

• If you have injected too much Insuman Basal, your blood sugar level may become too 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 treating hypoglycemia, see the box at the end of this leaflet.

If you forget to use Insuman Basal

• If you have missed a dose of Insuman Basalor if you have not injected enough insulin, your blood sugar level may rise too high (hyperglycemia). Check your blood sugar level frequently. For more information on treating hyperglycemia, see the box at the end of this leaflet.
• Do not take a double dose to make up for forgotten doses.

If you stop using Insuman Basal

This could lead to severe hyperglycemia (very high blood sugar levels) and ketoacidosis (increased acid in the blood because the body breaks down fat instead of sugar). Do not stop your treatment with Insuman Basal without consulting your doctor immediately, who will determine if you are truly allergic and advise you on what to do.

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

Insulin confusion

Always check the insulin label before each injection to avoid mix-ups between Insuman Basal and other insulins.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

More serious adverse effects

Adverse effects reported with low frequency(may affect up to 1 in 100 people)

• Severe allergic reactions with low blood pressure(shock)

Adverse effects reported with unknown frequency(frequency cannot be estimated from available data)

• The most frequent adverse effect is hypoglycemia (low blood sugar levels). Severe hypoglycemia can cause brain damage and can be life-threatening. For more information on adverse effects due to low or high blood sugar levels, see the box at the end of this prospectus.

• Severe allergic reactions to insulinmay occur, which could be life-threatening. These reactions to insulin or excipients can cause widespread skin reactions (rash and itching all over the body), severe swelling of the skin or mucous membranes (angioedema), difficulty breathing, a drop in blood pressure with rapid heartbeat, and sweating.

Other adverse effects

Adverse effects reported with frequency(may affect up to 1 in 10 people)

• Edema

Insulin treatment may cause temporary water retention in the body with swelling of the calves and ankles

• Injection site reactions

Adverse effects reported with low frequency

• Urticaria at the injection site (rash with itching)

Other adverse effects reported with unknown frequency

• Sodium retention
• Ocular reactions

A significant change (improvement or worsening) in the control of your blood sugar level can temporarily alter your vision. If you have proliferative retinopathy (an eye disease related to diabetes), severe hypoglycemic attacks can cause temporary loss of vision.

• Changes in the skin at the injection site.

If insulin is injected too frequently in the same place, the fatty tissue can shrink (lipoatrophy) or become thicker (lipohypertrophy). Lumps under the skin can also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis). Insulin may not work very well if injected into a lumpy area. Change the injection site to help avoid these skin changes.

• Skin and allergic reactions

Moderate allergic reactions may occur at the injection site (such as redness, pain, especially intense when injecting, itching, urticaria, swelling, or inflammation). These reactions can also spread around the injection site. Most mild reactions to insulins usually resolve on their own within a few days or weeks.

• Antibodies to insulin

Insulin treatment may cause the body to produce antibodies against insulin (substances that act against insulin). However, this will only require modifying your insulin dose in rare cases.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Annex V.

By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Insuman Basal

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

Do not use this medicine after the expiration date stated on the packaging and on the label of the vial after "EXP". The expiration date is the last day of the month indicated.

Unopened vials

Store in a refrigerator (between 2°C and 8°C). Do not freeze. Do not place Insuman Basal near the freezer compartment or next to a cold accumulator.

Keep the vial in the outer packaging to protect it from light.

Opened vials

Once in use, the vial can be stored for a maximum of 4 weeks in the outer packaging at a temperature not exceeding 25°C and protected from direct heat (e.g., next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this period. It is recommended to note the date of the first use of the vial on the label.

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

6. Package Contents and Additional Information

Composition of Insuman Basal

• The active ingredient is human insulin. One ml of Insuman Basal contains 40 IU (International Units) of the active ingredient human insulin.
• The other components are: protamine sulfate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2, "Important information about some of the components of Insuman Basal"), hydrochloric acid (for pH adjustment), and water for injectable preparations.

Appearance of the Product and Package Size

After mixing, Insuman Basal is a uniform, milky liquid (injectable suspension), without lumps, particles, or visible flocculation.

Insuman Basal is presented in vials containing 10 ml of suspension (400 IU). It is presented in packages of 1 and 5 vials of 10 ml. Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D‑65926 Frankfurt am Main

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

Date of the last revision of this prospectus:

Other sources of information

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

HYPERGLYCEMIA AND HYPOGLYCEMIA

Always carry something sweet with you (at least 20 grams)

Always carry some information that indicates you are diabetic

HYPERGLYCEMIA (high blood sugar levels)

If you have very high blood sugar levels (hyperglycemia),you may not have injected enough insulin.

Why do you get hyperglycemia?

Some examples are:

• you did not inject your insulin or did not inject enough, or if its effect has decreased, for example, due to incorrect storage,
• you are doing less exercise than usual, you are under stress (emotional distress, nervousness), or you are suffering from an injury, surgery, infection, or fever,
• you are using or have used certain medications (see section 2, "Other medicines and Insuman Basal").

Warning symptoms of hyperglycemia

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

What should you do if you suffer from hyperglycemia?

You should analyze your blood sugar level and your acetone level in the urine as soon as you experience any of these symptoms.Hyperglycemia or severe ketoacidosis should always be treated by a doctor, usually in a hospital.

HYPOGLYCEMIA (low blood sugar levels)

If your blood sugar level drops too low, you may lose consciousness. Severe hypoglycemia can cause a heart attack or brain damage and can be life-threatening. You should usually be able to recognize when your blood sugar level is dropping too low to take the necessary measures.

Why do you get hypoglycemia?

Some examples are:

• you inject too much insulin,
• you miss meals or delay them,
• you do not eat enough, or you eat foods that contain less carbohydrates than usual (sugars and similar substances are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),
• you lose carbohydrates due to vomiting or diarrhea,
• you drink alcohol, especially if you are not eating much,
• you are doing more exercise 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 using or have used certain medications (see section 2, "Other medicines and Insuman Basal").

It is also more likely to occur hypoglycemia if:

• you have just started insulin treatment or changed to another insulin preparation,
• your blood sugar levels are almost normal or are unstable,
• you change the skin site where you inject insulin (e.g., from the thigh to the upper arm),
• you have severe kidney or liver disease, or other diseases such as hypothyroidism.

Warning symptoms of hypoglycemia

• In your body

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

• In your brain

Examples of symptoms that indicate low blood sugar in the brain: headaches, intense hunger, nausea, vomiting, fatigue, drowsiness, sleep disorders, restlessness, aggressive behavior, concentration problems, altered reactions, depression, confusion, speech disorders (sometimes, complete loss of speech), visual disturbances, tremors, paralysis, tingling sensations (paresthesias), numbness and tingling sensations in the mouth area, dizziness, loss of self-control, feeling of helplessness, seizures, loss of consciousness.

The first warning symptoms of hypoglycemia ("warning symptoms") may change, weaken, or be absent if

• you are an elderly person, have had diabetes for a long time, or suffer from a certain type of nerve disease (autonomic diabetic neuropathy),
• you have recently experienced a hypoglycemic episode (e.g., the day before) or if it develops gradually,
• you have almost normal or, at least, much improved blood sugar levels,
• you have recently changed from an animal insulin to a human insulin like Insuman,
• you are using or have used certain medications (see section 2, "Other medicines and Insuman Basal").

In this case, you may experience severe hypoglycemia (and even lose consciousness) before you realize the problem. Always be familiar with your warning symptoms. If necessary, more frequent blood sugar analysis can help identify mild hypoglycemic episodes that would otherwise go unnoticed. If you are not sure you can recognize your warning symptoms, avoid situations (such as driving a car) that could put you or others in danger due to hypoglycemia.

What should you do if you suffer from hypoglycemia?

1. Do not inject insulin. Immediately ingest 10 to 20 grams of sugar, such as glucose, sugar cubes, or a sugary drink. Note: Artificial sweeteners and sugar-free products do not help treat hypoglycemia.
2. Then, eat something that increases your blood sugar level in the long term (such as bread or pasta). Your doctor or nurse should have discussed this with you beforehand.
3. If hypoglycemia recurs, take another 10 to 20 grams of sugar.
4. Consult a doctor immediately if you are unable to control hypoglycemia or if it recurs.

Tell your family, friends, or people close to you:

If you are unable to swallow or lose consciousness, you will need an injection of glucose or glucagon (a medication that increases blood sugar levels). These injections are justified even if you are not sure you have hypoglycemia.

It is recommended to analyze your blood sugar level immediately after ingesting glucose to confirm that you actually have hypoglycemia.