Humulin

Package leaflet: Information for the user

HUMULIN R (Regular) 100 UI/ml solution for injection in vial

(human insulin)
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 others, 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, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Humulin R is and what it is used for

The active substance in Humulin R is human insulin, which is used in the treatment of diabetes.
Diabetes is a disease that arises when the pancreas does not produce enough insulin to
control blood glucose levels. Humulin R is used to control glucose levels over the long term. Humulin R is a rapid-acting insulin preparation.
Your doctor may prescribe Humulin R together with a long-acting insulin.
Each type of insulin comes with its own package leaflet containing information for its correct use. Do not change the type of insulin unless instructed by your doctor. Be very careful when changing the type of insulin. Each type of insulin has a different colour and symbol on the packaging and vial so that you can easily see the difference.

2. What you need to know before using Humulin R

Do not use Humulin R

• If you think you are experiencing hypoglycaemia (low blood sugar levels). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section A in paragraph 4).
• If you are allergic to human insulin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or diabetes nurse before using Humulin R.

• If your blood glucose levels are well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar levels are dropping too low. The warning signs are listed later in this leaflet. You must pay careful attention to meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar levels regularly by frequent testing.

• Some people who have experienced hypoglycaemia (low blood sugar) after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemic reactions were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.

• If you answer YES to any of the following questions, inform your doctor, pharmacist, or diabetes centre nurse:

  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
  • Your insulin requirements may change if you consume alcohol.

• Also inform your doctor, pharmacist, or diabetes centre nurse if you are planning to travel abroad. Differences in time zones between countries may require adjustments to your insulin injection and meal schedules compared to when you are at home.

• Some patients with long-standing type 2 diabetes mellitus and heart disease or a history of stroke who were treated with pioglitazone and insulin have reported the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (oedema).

Skin changes at the injection site:
You should rotate your injection sites 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 Humulin R"). If you currently inject into an area with lumps, consult your doctor before starting to inject in another area. Your doctor may advise you to monitor your blood glucose more closely and adjust your insulin dose or other antidiabetic medications.

For athletes: Using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and Humulin R
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Your insulin requirements may change if you are taking:

• glucocorticoids
• thyroid hormone replacement therapy
• oral hypoglycaemics (antidiabetic medicines)
• acetylsalicylic acid (aspirin)
• growth hormone
• octreotide, lanreotide
• beta-stimulants (e.g. ritodrine, salbutamol, terbutaline)
• beta-blockers
• thiazides and certain antidepressants (monoamine oxidase inhibitors)
• danazol
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g. captopril, enalapril) or angiotensin II receptor antagonists.

Pregnancy, breastfeeding and fertility
Insulin requirements usually decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet.
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines
Your ability to concentrate and react may be reduced if you experience a hypoglycaemic reaction (low blood sugar). Be aware of this potential problem in any situation where you could put yourself or others at risk (e.g. driving a vehicle or operating machinery).
You should consult your diabetes nurse or doctor about whether it is safe for you to drive if you:

• frequently experience episodes of hypoglycaemia
• have reduced or absent warning signs of hypoglycaemia

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

3. How to use Humulin R

Always check the packaging and label of the vial to confirm the name and type of insulin
dispensed to you by the pharmacist. Ensure that the Humulin package corresponds to the one
prescribed by your doctor.
Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.

Dosage

• Follow your doctor's instructions precisely regarding dose amount, timing, and frequency of administration. These instructions are specific to you. Follow them exactly and have your condition regularly monitored at the diabetes care center.
• If you switch the type of insulin you are using (for example, from animal insulin to human insulin), you may need a different dose (higher or lower) than before. This change may occur with the very first injection, or it may be adjusted gradually over several weeks or months.
• Inject Humulin R subcutaneously. You should administer an intramuscular injection only if specifically instructed by your doctor.

Preparation of Humulin R

• Humulin R is already dissolved in water and must not be mixed. However, use it only if it appears like water. The solution must be clear, colourless, and free from solid particles. Check this before each injection.

Injection of Humulin R

• First, wash your hands.

• Before injecting, disinfect the skin according to the instructions you have received. Disinfect the rubber stopper of the vial as well, but do not remove it.

• Use a sterile syringe and needle to pierce the rubber stopper and draw up the required dose of Humulin R. Your doctor or diabetes care center will instruct you
  exactly how to do this. You must never share your syringes or needles with anyone else.

• Inject the medicine subcutaneously, as you have been taught. Do not inject it directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure the new injection site is at least one centimetre away from the previous one, and remember to rotate injection sites as instructed.

• Your doctor will tell you if you need to mix Humulin R with Humulin I. For example, if you need to inject a mixture, draw Humulin R into the syringe first, before drawing the long-acting insulin. Inject the mixture immediately after preparation. Repeat the same steps each time. Normally, you should not mix Humulin R with pre-mixed human insulins. Never mix Humulin R with insulins from other manufacturers or with animal insulins.

• Do not administer Humulin R intravenously. Inject Humulin R as taught by your doctor or nurse at the diabetes care center. Only your doctor may administer Humulin R intravenously, and only under special circumstances such as surgery or if you are ill and your blood glucose levels are too high.

If you use more Humulin R than you should
If you use more Humulin R than prescribed, your blood sugar level may drop too low.
Check your blood sugar level (see section 4, point A).
If you forget to use Humulin R
If you use less Humulin R than prescribed, your blood sugar level may rise too high.
Check your blood sugar level. Do not inject a double dose to make up for a missed dose.
If you stop using Humulin R
If you use less Humulin R than prescribed, your blood sugar level may rise too high.
Do not change the type of insulin unless instructed by your doctor.
If you have any doubts about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Human insulin may cause hypoglycaemia (low blood sugar level). See further information on hypoglycaemia below, in the subsection "Common diabetes problems".

Possible side effects
Systemic allergy is very rare (affects fewer than 1 in 10,000 people). Symptoms include:

• drop in blood pressure
• rash all over the body
• difficulty breathing
• shortness of breath
• rapid heartbeat
• sweating

If you think Humulin R is causing you this type of insulin allergy, tell your doctor immediately.

Local allergy is common (affects fewer than 1 in 10 people). In some people, the skin at the injection site may become red, swollen, and itchy. Usually, this reaction disappears within a few days or weeks. If this occurs, inform your doctor.

Skin changes at the injection site:
If you inject insulin too often in the same spot, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy) (may affect up to 1 in 100 people). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency is unknown). Insulin may not work well if you inject into an area with lumps. Change your injection site with each injection to prevent these skin changes.

Oedema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving glycaemic control.

Common diabetes problems

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means that there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• an excessive dose of Humulin R or another insulin;
• a delayed or missed meal, or a change in diet;
• excessive physical exercise or work performed immediately before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• a change in insulin requirement;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.

Usually, the first symptoms of hypoglycaemia appear quickly and include:

• tiredness
• rapid heartbeat
• nervousness or restlessness
• discomfort
• headache
• cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations such as driving a vehicle, in which hypoglycaemia could put you or others at risk.
Do not use Humulin R if you think you are experiencing hypoglycaemia (low blood sugar level).

If your blood sugar level is low, eat glucose tablets, sugar, or drink a sugary drink. Then eat some fruit, biscuits, or a sandwich, as your doctor has advised, and rest. Often this is sufficient to counteract mild hypoglycaemia or a minor insulin overdose. If you notice that your condition worsens and you have shortness of breath and pale skin, inform your doctor immediately. An injection of glucagon can treat moderately severe hypoglycaemia. Take glucose or sugar after the glucagon injection. If you do not respond to glucagon, you must be admitted to hospital. Ask your doctor for information on the use of glucagon.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means that your body does not have enough insulin. Hyperglycaemia may be caused by:

• missing a dose of Humulin R or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:

• drowsiness
• loss of appetite
• flushed face
• fruity breath odour
• thirst
• feeling unwell

Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical assistance.

Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death.

Three simple actions to avoid hypoglycaemia or hyperglycaemia are:

• Always keep spare syringes and a vial of Humulin R available.
• Always carry identification indicating that you are diabetic.
• Always carry some sugar with you.

C. Illnesses
If you are ill, especially if you feel unwell or are sick, your insulin requirement may change. Even when you are not eating normally, you still need insulin. Test your urine and blood; when unwell, follow the precautions you already know and inform the nurse at your diabetes clinic or your doctor.

Reporting of side effects
If you get 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 [national reporting system]. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humulin R

Keep this medicine out of the sight and reach of children.
Before use, store Humulin R in a refrigerator (2°C - 8°C). Do not freeze.
Once in use, the vial may be stored at room temperature (below 30°C) for up to 28 days. Do not place it near a heat source or in direct sunlight.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of that month.
Do not use this medicine if it appears discolored or contains solid particles. Use it only if it looks like water. Check this before each injection.
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 Humulin R contains

• The active substance is human insulin. Human insulin is produced in the laboratory using a technology called "recombinant DNA". It has the same structure as the natural hormone produced by the pancreas. Therefore, it differs from animal insulins.
• The excipients are metacresol, glycerol, and water for injections. Sodium hydroxide or hydrochloric acid may have been used during the manufacturing process to adjust the pH.

Description of the appearance of Humulin R and contents of the pack
Humulin R (Regular) 100 IU/ml solution for injection is a sterile, clear, colourless aqueous solution containing 100 units of insulin per millilitre (100 IU/ml). Each vial contains 1,000 units (10 millilitres).
Humulin R 100 IU/ml is available in packs containing 1 vial, 2 vials, or in a multiple pack containing 5 vials (comprising 5 packs of 1 vial each).
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
The Marketing Authorization is held by Eli Lilly Italia S.p.A., Via Gramsci 731/733 - 50019 Sesto Fiorentino (FI), Italy.
Humulin R in vials is manufactured by:

• Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain
• Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Huminsulin „Lilly“ Normal (Austria)
Umuline rapide 100 IU/ml (France)
Humuline Regular (Belgium, Luxembourg)
Huminsulin Normal 100 (Germany)
Humulin Regular (Denmark, Greece, Sweden)
Humulina Regular (Spain)
Humulin S (Ireland, United Kingdom)
Humulin R (Czech Republic, Italy, Romania)

Package leaflet: Information for the user

HUMULIN I (Isophane) 100 IU/ml injectable suspension in a vial

(human insulin)
Please read this leaflet carefully 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 others, even if their symptoms are the same as yours, as it could be harmful.
• If any adverse reaction occurs, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Humulin I is and what it is used for

The active substance in Humulin I is human insulin, which is used in the treatment of diabetes.
Diabetes is a disease caused by the pancreas not producing enough insulin to adequately control blood glucose levels.
Humulin I is used to control glucose levels over the long term. Its prolonged action is due to the presence of protamine sulfate in the suspension.
Your doctor may prescribe Humulin I along with a rapid-acting insulin. Each type of insulin comes with its own package leaflet containing information for its correct use. Do not change the type of insulin unless instructed by your doctor. Be very careful when switching from one type of insulin to another. Each type of insulin has a different colour and symbol on the packaging and vial so that you can easily distinguish the differences.

2. What you need to know before using Humulin I

Do not use Humulin I

• If you think you are experiencing hypoglycaemia (low blood sugar levels). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section A in paragraph 4).
• If you are allergic to human insulin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Humulin I.

• If your blood glucose levels are well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar levels are dropping too low. The warning signs are listed later in this leaflet. You must pay careful attention to meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar levels frequently.

• Some people who have experienced hypoglycaemia (low blood sugar levels) after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemic reactions were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.

• If you answer YES to any of the following questions, inform your doctor, pharmacist, or nurse at the diabetes centre:

  • Have you been ill recently?
  • Do you have liver or kidney problems?
  • Are you doing more physical exercise than usual?
  • Your insulin requirements may change if you consume alcohol.
  • Also inform your doctor, pharmacist, or nurse at the diabetes centre if you are planning to travel abroad. Differences in time zones between countries may require adjustments to your insulin injection and meal schedules compared to your routine at home.

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

Skin changes at injection site:
You should rotate your injection sites 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 Humulin I"). If you currently inject into an area with lumps, consult your doctor before switching to a new injection site. Your doctor may ask you to monitor your blood glucose levels more closely and may adjust your insulin dose or other antidiabetic medications.

For athletes: Using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and Humulin I
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Your insulin requirements may change if you are taking:

• glucocorticoids
• thyroid hormone replacement therapy
• oral hypoglycaemics (antidiabetic medicines)
• acetylsalicylic acid (aspirin)
• growth hormone
• octreotide, lanreotide
• beta-stimulants (e.g., ritodrine, salbutamol, terbutaline)
• beta-blockers
• thiazides and certain antidepressants (monoamine oxidase inhibitors)
• danazol
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril) or angiotensin II receptor antagonists.

Pregnancy, breastfeeding and fertility
Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or your diet.
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines
Your ability to concentrate and react may be impaired if you experience a hypoglycaemic reaction (low blood sugar levels). Be aware of this potential problem in any situation where you could place yourself or others at risk (e.g., driving a vehicle or operating machinery). You should consult your diabetes nurse or doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia
• have reduced or absent warning symptoms of hypoglycaemia

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

3. How to use Humulin I

Always check the packaging and label of the vial for the name and type of insulin
supplied to you by the pharmacist. Make sure that the Humulin package corresponds to the one
prescribed by your doctor.
Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Dosage

• Humulin I is normally administered as basal insulin. Follow your doctor's instructions precisely regarding dose, timing, and frequency of administration—these instructions are specific to you. Follow them exactly and have regular check-ups at your diabetes care center.
• If you switch from one type of insulin to another (for example, from animal insulin to human insulin), you may require a different dose (either higher or lower) than before. This change may occur with the first injection or may be introduced gradually over several weeks or months.
• Inject Humulin I subcutaneously. This medicine must not be administered by any other route. Under no circumstances should Humulin I be administered intravenously.

Preparation of Humulin I

• Before use, gently roll the vial containing Humulin I between the palms of your hands several times to resuspend the insulin completely, until the solution appears uniformly cloudy or milky. If this does not occur, repeat the procedure until the contents are fully mixed. Do not shake vigorously, as this may cause foaming, which could interfere with accurate dose measurement. Inspect vials frequently and do not use if floating residues or white particles adhering to the bottom or walls of the vial are observed, as these give the vial a frost-like appearance. Check for these signs before each injection.

Injection of Humulin I

• First, wash your hands.
• Before injecting, disinfect the skin according to the instructions you have received. Also disinfect the rubber stopper of the vial, but do not remove it.
• Use a sterile syringe and needle to pierce the rubber stopper and withdraw the required dose of Humulin I. Your doctor or diabetes care center will instruct you on the correct procedure. You must never share your syringes or needles with anyone else.
• Inject the medicine subcutaneously, as instructed. Do not inject directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure each injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.
• Your doctor will tell you if you need to mix Humulin R with Humulin I. For example, if a mixture is required, draw Humulin R into the syringe first, before drawing the long-acting insulin. Inject the mixture immediately after preparation. Repeat the same steps each time. Normally, do not mix Humulin I with pre-mixed human insulins. Never mix Humulin I with insulins from other manufacturers or with animal insulins.
• Humulin I must not be administered intravenously. Inject Humulin I exactly as shown to you by your doctor or the nurse at the diabetes care center.

If you use more Humulin I than you should
If you use more Humulin I than prescribed, your blood sugar level may drop (hypoglycemia).
Check your blood sugar level (see section A in paragraph 4).

If you forget to use Humulin I
If you use less Humulin I than prescribed, your blood sugar level may rise (hyperglycemia).
Check your blood sugar level. Do not inject a double dose to make up for the missed dose.

If you stop using Humulin I
If you use less Humulin I than prescribed, your blood sugar level may rise.
Do not change the type of insulin unless instructed by your doctor.

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

4. Possible side effects

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

Human insulin can cause hypoglycaemia (low blood sugar level). See further information on hypoglycaemia below, in the subsection “Common problems of diabetes”.

Possible side effects

Systemic allergy is very rare (affects fewer than 1 in 10,000 people). Symptoms include:

• drop in blood pressure
• skin rash all over the body
• difficulty breathing
• shortness of breath
• rapid heartbeat
• sweating

If you think Humulin I is causing you this type of insulin allergy, inform your doctor immediately.

Local allergy is common (affects fewer than 1 in 10 people). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.

Skin changes at the injection site:
If you inject insulin too often in the same spot, the fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy) (may affect up to 1 in 100 people). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency is unknown). Insulin may not work properly if you inject into an area with lumps. Change your injection site with each injection to prevent these skin changes.

Oedema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving glycaemic control.

Common problems of diabetes

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means that there is not enough sugar in the blood. Hypoglycaemia can be caused by:

• an excessive dose of Humulin I or another insulin;
• a delayed or missed meal, or a change in diet;
• excessive physical exercise or work performed immediately before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• a change in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycaemia appear rapidly and include:

• tiredness
• rapid heartbeat
• nervousness or restlessness
• malaise
• headache
• cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.

Do not use Humulin I if you think you are experiencing hypoglycaemia (low blood sugar level).

If your blood sugar level is low, eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich, as your doctor has advised, and rest. Often this is sufficient to counteract mild hypoglycaemia or a minor insulin overdose. If you notice that your condition worsens, and you experience shortness of breath and pale skin, inform your doctor immediately. An injection of glucagon can treat moderately severe hypoglycaemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information about the use of glucagon.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means that there is not enough insulin in your body. Hyperglycaemia can be caused by:

• missing a dose of Humulin I or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia may lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:

• drowsiness
• loss of appetite
• flushed face
• fruity-smelling breath
• thirst
• feeling unwell

Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical help.

Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death.

Three simple measures to avoid hypoglycaemia or hyperglycaemia are:

• Always keep spare syringes and a vial of Humulin I available
• Always carry identification indicating that you are diabetic
• Always carry sugar with you

C. Illnesses
If you are ill, especially if you feel unwell or are unwell, your insulin requirement may vary. Even when you are not eating normally, you still need insulin. Test your urine and blood; when unwell, follow the precautions you already know and inform your diabetes nurse or doctor.

Reporting of side effects
If you get 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. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humulin I

Keep this medicine out of the sight and reach of children.
Before use, store Humulin I in the refrigerator (2°C - 8°C). Do not freeze. During use,
store the vial at room temperature (below 30°C) for up to 28 days. Do not place near heat sources or direct sunlight.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of that month.
Do not use this medicine if you notice floating residues or white particles adhering to the bottom or walls of the vial, which give it a frost-like appearance. Check for this before each injection.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Humulin I contains

• The active substance is human insulin. Human insulin is produced in the laboratory using a technology called "recombinant DNA". It has the same structure as the natural hormone produced by the pancreas and is therefore different from animal insulins. The human insulin present in Humulin I is available in a suspension together with protamine sulfate.
• The excipients are protamine sulfate, metacresol, phenol, glycerol, disodium phosphate 7H₂O, zinc oxide and water for injections. Sodium hydroxide or hydrochloric acid may have been used during the manufacturing process to adjust the pH.

Description of the appearance of Humulin I and contents of the pack
Humulin I (Isophane) 100 IU/ml injectable suspension is a sterile white suspension containing
100 units of insulin per millilitre (100 IU/ml). Each vial contains 1,000 units (10 millilitres).
Humulin I 100 IU/ml is available in packs containing 1 vial, 2 vials or a multiple pack containing 5 vials (comprising 5 packs of 1 vial each).
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
The Marketing Authorisation is held by Eli Lilly Italia S.p.A., Via Gramsci 731/733 - 50019 Sesto Fiorentino (FI), Italy.
Humulin I in vials is manufactured by:

• Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain
• Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France

This medicinal product is authorised in the European Economic Area Member States under the following names:
Huminsulin „Lilly“ Basal (Austria)
Humuline NPH (Belgium, Luxembourg)
Humulin N (Czech Republic)
Huminsulin Basal (NPH) 100 (Germany)
Humulin NPH (Denmark, Greece, Sweden)
Humulina NPH (Spain)
Humulin I (Ireland, Italy, United Kingdom)
Umuline NPH (France)

Package leaflet: Information for the user

HUMULIN 30/70 (Premixed) 100 IU/ml injectable suspension in a vial

(human insulin)
Please read this leaflet carefully 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, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Never give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Humulin 30/70 is and what it is used for
2. What you need to know before using Humulin 30/70
3. How to use Humulin 30/70
4. Possible side effects
5. How to store Humulin 30/70
6. Contents of the pack and other information

1. What Humulin 30/70 is and what it is used for

The active substance in Humulin 30/70 is human insulin, which is used in the treatment of diabetes.
Diabetes is a condition in which the pancreas does not produce enough insulin to properly control blood glucose levels. Humulin 30/70 is used to control blood glucose over the long term. It is a premixed suspension of rapid-acting insulin and prolonged-acting insulin. Its prolonged action is due to the presence of protamine sulfate in the suspension.
Your doctor may prescribe Humulin 30/70 or another type of prolonged-acting insulin.
Each type of insulin comes with its own package leaflet containing information for correct use. Do not change the type of insulin unless instructed by your doctor. Be very careful when switching from one type of insulin to another. Each type of insulin has a different colour and symbol on the packaging and vial so that you can easily distinguish between them.

2. What you need to know before using Humulin 30/70

Do not use Humulin 30/70

• If you think you are experiencing hypoglycaemia (low blood sugar levels). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section A in section 4).
• If you are allergic to human insulin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse at the diabetes centre before using Humulin 30/70.

• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet. You must pay close attention to meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar levels frequently by regular testing.
• Some people who have experienced hypoglycaemia (low blood sugar) after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist or nurse at the diabetes centre:
• Have you been ill recently?
• Do you have liver or kidney problems?
• Are you doing more physical exercise than usual?
• Your insulin requirements may change if you consume alcohol.
• Also inform your doctor, pharmacist or nurse at the diabetes centre if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal times compared to your usual routine at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of stroke who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (oedema).

Skin changes at the injection site:
Rotate your injection sites 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 Humulin 30/70"). If you currently inject into an area with lumps, consult your doctor before starting to inject in another area. Your doctor may advise you to monitor your blood glucose more closely and adjust your insulin dose or that of other antidiabetic medicines.

For athletes: using this medicine without a therapeutic need constitutes doping and may lead to a positive anti-doping test.

Other medicines and Humulin 30/70
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Your insulin requirements may change if you are taking:

• glucocorticoids
• thyroid hormone replacement therapy
• oral hypoglycaemics (antidiabetic medicines)
• acetylsalicylic acid (aspirin)
• growth hormone
• octreotide, lanreotide
• beta-stimulants (e.g. ritodrine, salbutamol, terbutaline)
• beta-blockers
• thiazides and certain antidepressants (monoamine oxidase inhibitors)
• danazol
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g. captopril, enalapril) or angiotensin II receptor antagonists.

Pregnancy, breast-feeding and fertility
Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breast-feeding, you may need to adjust your insulin dose or your diet.
If you are pregnant, breast-feeding, suspect you may be pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines
Your ability to concentrate and react may be reduced if you experience a hypoglycaemic reaction (low blood sugar). Keep this potential problem in mind in any situation where you might put yourself or others at risk (e.g. driving a vehicle or operating machinery). You should consult the nurse at the diabetes centre or your doctor about whether it is safe for you to drive if you:

• have frequent episodes of hypoglycaemia
• have reduced or absent warning signs of hypoglycaemia

Humulin 30/70 contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially "sodium-free".

3. How to use Humulin 30/70

Always check the packaging and label of the vial for the name and type of insulin
dispensed to you by the pharmacist. Make sure that the Humulin package corresponds to
the one prescribed by your doctor.
Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Dosage

• Follow your doctor's instructions precisely regarding dose amount, timing, and frequency of administration. These instructions apply specifically to you. Follow them exactly and have your condition monitored regularly at the diabetes clinic.
• If you change the type of insulin you are using (for example, from animal insulin to human insulin), you may require a different dose (higher or lower) than before. This change may occur with the first injection, or it may be introduced gradually over a period of several weeks or months.
• Inject Humulin 30/70 subcutaneously. This medicine must not be administered by any other route. Under no circumstances should Humulin 30/70 be administered intravenously.

Preparation of Humulin 30/70

• Before use, vials containing Humulin 30/70 must be rolled between the palms of the hands several times to completely resuspend the insulin, until it appears uniformly cloudy or milky. If this does not occur, repeat the procedure until the components are fully mixed. Do not shake vigorously, as this may cause foaming, which could interfere with accurate dose measurement. Vials should be inspected frequently and must not be used if
  floating particles or white deposits adhering to the bottom or sides of the vial are observed,
  giving it a frost-like appearance. Check this before each injection.

Injection of Humulin 30/70

• First, wash your hands.
• Before injecting, clean the skin according to the instructions you have received. Disinfect the rubber stopper of the vial, but do not remove it.
• Use a sterile syringe and needle to pierce the rubber stopper and withdraw the required amount of Humulin 30/70 to be injected. Your doctor or diabetes clinic will show you exactly how to do this. You must never share your syringes or needles with anyone else.
• Inject the medicine subcutaneously, as you have been taught. Do not inject directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure that each injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.

If you use more Humulin 30/70 than you should
If you use more Humulin 30/70 than prescribed, your blood sugar level may drop. Check your blood sugar level (see section A in paragraph 4).
If you forget to use Humulin 30/70
If you use less Humulin 30/70 than prescribed, your blood sugar level may rise. Check your blood sugar level. Do not inject a double dose to make up for a missed dose.
If you stop using Humulin 30/70
If you use less Humulin 30/70 than prescribed, your blood sugar level may rise. Do not change the type of insulin unless instructed by your doctor.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Human insulin may cause hypoglycaemia (low blood sugar level). See further information on hypoglycaemia below, in the subsection “Common problems of diabetes”.

Possible side effects
Systemic allergy is very rare (affects fewer than 1 in 10,000 people). Symptoms include:

• low blood pressure
• rash over the entire body
• difficulty breathing
• shortness of breath
• rapid heartbeat
• sweating

If you think Humulin 30/70 is causing this type of insulin allergy, inform your doctor immediately.

Local allergy is common (affects fewer than 1 in 10 people). In some individuals, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.

Skin changes at the injection site:
If you inject insulin too frequently in the same spot, fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy) (may affect up to 1 in 100 people). Lumps under the skin may also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis; frequency is unknown). Insulin may not work effectively if injected into an area with lumps. Change your injection site with each injection to prevent these skin changes.

Oedema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving glycaemic control.

Common problems of diabetes

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• an excessive dose of Humulin 30/70 or another insulin;
• a delayed or missed meal, or a change in diet;
• excessive physical exercise or work performed immediately before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• a change in insulin requirements;
• worsening of pre-existing kidney or liver disease.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the early symptoms of hypoglycaemia appear rapidly and include:

• tiredness
• rapid heartbeat
• nervousness or agitation
• malaise
• headache
• cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations such as driving a vehicle, in which hypoglycaemia could put you or others at risk.
Do not use Humulin 30/70 if you think you are experiencing hypoglycaemia (low blood sugar level).

If your blood sugar level is low, eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich, as advised by your doctor, and rest. Often this is sufficient to counteract mild hypoglycaemia or a modest insulin overdose. If you notice your condition worsening and experience shortness of breath and pale skin, inform your doctor immediately. An injection of glucagon can treat moderately severe hypoglycaemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information about the use of glucagon.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycaemia may be caused by:

• missing a dose of Humulin 30/70 or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or strong emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:

• drowsiness
• loss of appetite
• flushed face
• fruity-smelling breath
• thirst
• feeling unwell

Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical assistance.

Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death.

Three simple measures to avoid hypoglycaemia or hyperglycaemia are:

• Always keep spare syringes and a vial of Humulin 30/70 available
• Always carry identification indicating that you are diabetic
• Always carry sugar with you

C. Illness
If you are ill, especially if you feel unwell or are unwell, your insulin requirements may vary. Even when you are not eating normally, you still need insulin. Test your urine and blood; when unwell, follow the precautions you already know and inform the nurse at your diabetes clinic or your doctor.

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. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humulin 30/70

Keep this medicine out of the sight and reach of children.
Before use, store Humulin 30/70 in a refrigerator (2°C - 8°C). Do not freeze. Once in use,
store the vial at room temperature (below 30°C) for up to 28 days. Do not place near heat sources or direct sunlight.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of that month.
Do not use this medicine if you notice floating residues or white particles adhering to the bottom or walls of the vial, which may give it a frost-like appearance. Check this carefully before each injection.
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. Contents of the pack and other information

What Humulin 30/70 contains

• The active substance is human insulin. Human insulin is produced in the laboratory using a technology called "recombinant DNA". It has the same structure as the natural hormone produced by the pancreas. Therefore, it differs from animal insulins. Humulin 30/70 is a premixed suspension containing 30% insulin dissolved in aqueous solution and 70% insulin combined with protamine sulfate.
• The excipients are protamine sulfate, metacresol, phenol, glycerol, disodium phosphate heptahydrate, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may have been used during the manufacturing process to adjust the pH.

Description of the appearance of Humulin 30/70 and contents of the pack
Humulin 30/70 (Mix) 100 IU/ml injectable suspension is a sterile white suspension containing 100 insulin units per millilitre (100 IU/ml). Each vial contains 1,000 units (10 millilitres).
Humulin 30/70 100 IU/ml is available in packs containing 1 vial, 2 vials, or in a multiple pack containing 5 vials (comprising 5 packs of 1 vial each).
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
The marketing authorisation is held by Eli Lilly Italia S.p.A., Via Gramsci 731/733 - 50019 Sesto Fiorentino (FI), Italy.
Humulin 30/70 in vials is manufactured by:

• Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain
• Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France

This medicinal product is authorised in the European Economic Area countries under the following names:
Huminsulin „Lilly“ Profil III (Austria)
Humuline 30/70 (Belgium, Luxembourg)
Humulin M3 (Ireland, United Kingdom)
Humulin 30/70 (Italy)
Umuline profil 30 (France)
Humulin M3 (30/70) (Greece)
Humulina 30:70 (Spain)

Package leaflet: Information for the user

HUMULIN R (Regular) 100 IU/ml injection solution in cartridge

(human insulin)
Please read this leaflet carefully 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, consult 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 could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Humulin R is and what it is used for

The active substance in Humulin R is human insulin, which is used in the treatment of diabetes.
Diabetes is a condition that arises when the pancreas does not produce enough insulin to properly
control blood glucose levels. Humulin R is used to control glucose levels over the long term. Humulin R is a short-acting insulin preparation.
Your doctor may prescribe Humulin R together with a long-acting insulin.
Each type of insulin comes with its own package leaflet containing information for correct use. Do not change the type of insulin unless instructed by your doctor. Be very careful when switching from one type of insulin to another. Each type of insulin has a different colour and symbol on the packaging and cartridge to help you easily distinguish between them.

2. What you need to know before using Humulin R

Humulin R in cartridges is suitable only for subcutaneous injection with a reusable pen.
Talk to your doctor if you need to inject insulin by another method.
Do not use Humulin R

• If you think you are experiencing hypoglycemia (low blood sugar). Instructions for managing mild hypoglycemia are provided later in this leaflet (see Section A in paragraph 4 ).
• If you are allergic to human insulin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Humulin R.

• If your blood glucose level is well controlled with your current insulin therapy, you may not notice the warning symptoms when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet. You must pay close attention to meal timing, frequency, and intensity of physical exercise. You should also monitor your blood sugar level frequently.
• Some people who have experienced hypoglycemia (low blood sugar) after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycemia were less noticeable or different. If you frequently experience hypoglycemia or have difficulty recognizing it, discuss this with your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist, or nurse at the diabetes center.
• Have you been ill recently?
• Do you have liver or kidney problems?
• Are you exercising more than usual?
• Your insulin requirements may change if you consume alcohol.
• Also inform your doctor, pharmacist, or diabetes center nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal schedules compared to when you are at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of stroke who were 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 unusual shortness of breath, rapid weight gain, or localized swelling (edema).

Skin changes at the injection site:
You must rotate your injection site 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 Humulin R"). If you currently inject into an area with lumps, consult your doctor before starting to inject in another area. Your doctor may ask you to monitor your blood glucose more closely and adjust your insulin dose or other antidiabetic medications.

For athletes: The use of this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and Humulin R
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Your insulin requirements may change if you are taking:

• glucocorticoids
• thyroid hormone replacement therapy
• oral hypoglycemics (antidiabetic medicines)
• acetylsalicylic acid (aspirin)
• growth hormone
• octreotide, lanreotide
• beta-stimulants (e.g., ritodrine, salbutamol, terbutaline)
• beta-blockers
• thiazides and certain antidepressants (monoamine oxidase inhibitors)
• danazol
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril) or angiotensin II receptor antagonists.

Pregnancy, breastfeeding, and fertility
Insulin requirements usually decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet.
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines
Your ability to concentrate and react may be reduced if you experience a hypoglycemic reaction (low blood sugar). Be aware of this potential problem in any situation where you could put yourself or others at risk (e.g., driving a vehicle or operating machinery). Consult your diabetes center nurse or doctor about whether it is safe for you to drive if you have:

• frequent episodes of hypoglycemia
• reduced or absent warning signs of hypoglycemia

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

3. How to use Humulin R

The 3 ml cartridge must only be used with 3 ml pens. Do not use with 1.5 ml pens.
Always check the packaging and the label of the cartridge for the name and type of insulin
provided to you by the pharmacist. Make sure the Humulin package matches the one
prescribed by your doctor.
Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. To prevent possible transmission of diseases, each cartridge must be used only by you, even if the needle on the delivery device is changed.

Dosage

• Follow your doctor's instructions exactly regarding amount, timing, and frequency of administration—these instructions are specific to you. Follow them precisely and have your condition monitored regularly at the diabetes clinic.
• If you change the type of insulin you are using (e.g., from animal insulin to human insulin), you may require a different dose (higher or lower) than before. This change may occur with the first injection or may be gradually adjusted over several weeks or months.
• Humulin R in cartridges is intended only for subcutaneous injection using a reusable insulin pen. Speak with your doctor if you need to administer insulin by another method.

Preparation of Humulin R

• Humulin R is already dissolved in water and must not be mixed. However, use it only if it appears like water. The solution must be clear, colorless, and free of solid particles. Check this before each injection.

Preparing the pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• You must use Humulin R cartridges only with Lilly insulin pens to ensure correct dose delivery.
• Follow the instructions provided with the pen. Insert the cartridge into the pen.
• Set the dose to 1 or 2 units. Then hold the pen with the attached needle pointing upward and gently tap the side of the pen to bring air bubbles to the top. With the pen still pointing upward, press the injection button until a drop of Humulin R appears at the needle tip. Small air bubbles may remain in the pen; these are not dangerous, but if they are too large, they may affect the accuracy of the dose.

Injecting Humulin R

• Before injecting, clean your skin as instructed.
• Inject the medicine subcutaneously, as you have been taught. Do not inject directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure each injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.
• Do not administer Humulin R intravenously. Inject Humulin R as taught by your doctor or nurse at the diabetes clinic. Only a doctor may administer Humulin R intravenously, and only under special circumstances such as surgery or illness with very high blood glucose levels.

After injection

• Immediately after completing the injection, remove the needle using the needle's outer cap. This helps keep Humulin R sterile, prevents leakage of the medicine, stops air from entering the pen, and helps prevent needle blockage. Never share your needles or your pen with others. Replace the cap on the pen.

Subsequent injections

• Leave the cartridge in the pen. Before each subsequent injection, select 1 or 2 units and press the injection mechanism while holding the pen upward until a drop of Humulin R appears at the needle tip. You can estimate how much Humulin R remains in the cartridge by observing the level through the side of the cartridge. Each line corresponds to approximately 20 units. If there is not enough insulin left for the next dose, replace the cartridge.

Do not mix any other insulin into a Humulin R cartridge. Once the cartridge is
empty, do not reuse it.
If you use more Humulin R than you should
If you use more Humulin R than prescribed, your blood sugar level may drop too low.
Check your blood sugar level (see section A in paragraph 4).
If you forget to use Humulin R
If you use less Humulin R than prescribed, your blood sugar level may rise.
Check your blood sugar level. Do not inject a double dose to make up for a missed dose.
If you stop using Humulin R
If you use less Humulin R than prescribed, your blood sugar level may rise.
Do not change the type of insulin unless directed by your doctor.
If you have any questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Human insulin may cause hypoglycaemia (low blood sugar level). See further information on hypoglycaemia below, in the subsection "Common diabetes-related problems".

Possible side effects

Systemic allergy is very rare (affects fewer than 1 in 10,000 people). Symptoms include:

• low blood pressure
• skin rash all over the body
• difficulty breathing
• shortness of breath
• rapid heartbeat
• sweating

If you think Humulin R is causing you this type of insulin allergy, inform your doctor immediately.

Local allergy is common (affects fewer than 1 in 10 people). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.

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 100 people). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency is unknown). Insulin may not work properly if injected into an area with lumps. Change your injection site with each injection to prevent these skin changes.

Oedema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving blood glucose control.

Common diabetes-related problems

A. Hypoglycaemia

Hypoglycaemia (low blood sugar level) means that there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• taking too high a dose of Humulin R or another insulin;
• delaying or missing a meal, or a change in diet;
• excessive exercise or physical work performed just before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• changes in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar level.

Usually, the first symptoms of hypoglycaemia appear quickly and include:

• tiredness
• rapid heartbeat
• nervousness or restlessness
• malaise
• headache
• cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations such as driving a vehicle, in which hypoglycaemia could put you or others at risk.

Do not use Humulin R if you think you are experiencing hypoglycaemia (low blood sugar level).

If your blood sugar level is low, eat glucose tablets, sugar, or drink a sugary drink. Then eat some fruit, biscuits, or a sandwich, as your doctor has advised, and rest. Often this is sufficient to counteract mild hypoglycaemia or a minor insulin overdose. If you notice that your condition worsens, and you experience shortness of breath and pale skin, inform your doctor immediately. An injection of glucagon can treat moderately severe hypoglycaemia. Take glucose or sugar after a glucagon injection. If you do not respond to glucagon, you must be admitted to hospital. Ask your doctor for information about the use of glucagon.

B. Hyperglycaemia and diabetic ketoacidosis

Hyperglycaemia (too much sugar in the blood) means that your body does not have enough insulin. Hyperglycaemia may be caused by:

• missing a dose of Humulin R or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or strong emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. Early symptoms develop slowly over several hours or days. They include:

• drowsiness
• loss of appetite
• flushed face
• fruity-smelling breath
• thirst
• feeling unwell

Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical assistance.

Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death.

Three simple measures to help prevent hypoglycaemia or hyperglycaemia are:

• Always keep spare syringes and a vial of Humulin R available
• Always carry identification indicating that you are diabetic
• Always carry sugar with you

C. Illness

If you are ill, especially if you feel unwell or are sick, your insulin requirements may change. Even when you are not eating normally, you still need insulin. Test your urine and blood; when unwell, follow the precautions you already know and inform your diabetes nurse or doctor.

Reporting of side effects

If you get 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. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humulin R

Keep this medicine out of the sight and reach of children.
Before use, store Humulin R in the refrigerator (2°C - 8°C). Do not freeze. During use,
store the pen and cartridge at room temperature (below 30°C) for up to 28 days. Do not store the pen and cartridges you are currently using in the refrigerator. Do not place the product near heat sources or direct sunlight.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of that month.
Do not use this medicine if you notice it is discolored or contains solid particles. You should use it only if its appearance is clear and similar to water. Check this before each injection.
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 Humulin R contains

• The active substance is human insulin. Human insulin is produced in the laboratory using a technology called "recombinant DNA". It has the same structure as the natural hormone produced by the pancreas. Therefore, it differs from animal insulins.
• The excipients are metacresol, glycerol, and water for injections. Sodium hydroxide or hydrochloric acid may have been used during the manufacturing process to adjust the pH.

Description of the appearance of Humulin R and contents of the pack
Humulin R (Regular) 100 IU/ml solution for injection is a sterile, clear, colourless aqueous solution containing 100 units of insulin per millilitre (100 IU/ml). Each cartridge contains 300 units (3 millilitres).
Cartridges are available in packs of 5 and 10.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
The marketing authorisation is held by Eli Lilly Italia S.p.A., Via Gramsci 731/733, 50019 Sesto Fiorentino (FI), Italy.
Humulin R in cartridges is manufactured by:
Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France
Eli Lilly Italia S.p.A., Via A. Gramsci, 731-733, 50019 Sesto Fiorentino, Italy

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Huminsulin „Lilly“ Normal (Austria)
Umuline Rapide 100 IU/ml (France)
Humuline Regular (Belgium, Luxembourg, Netherlands)
Huminsulin Normal für Pen 3 ml (Germany)
Humulin Regular (Cyprus, Greece, Portugal, Sweden)
Humulin S (Malta, Ireland, United Kingdom)
Humulin R (Bulgaria, Croatia, Estonia, Hungary, Latvia, Lithuania, Italy, Poland, Romania, Slovenia)
Humulin R Cartridge (Czech Republic, Slovakia)

Package leaflet: Information for the user

HUMULIN I (Isophane) 100 IU/ml suspension for injection in cartridge

(human insulin)
Please read this leaflet carefully 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 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, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Humulin I is and what it is used for

The active substance contained in Humulin I is human insulin, which is used in the treatment of diabetes.
Diabetes is a condition that arises when the pancreas does not produce enough insulin to adequately
control blood glucose levels. Humulin I is used to control glucose levels over the long term. Its prolonged action
is due to the presence of protamine sulfate in the suspension.
Your doctor may prescribe Humulin I alone or in combination with a rapid-acting insulin. Each type of insulin
is packaged with its own patient information leaflet containing instructions for proper use. Do not change
the type of insulin unless directed by your doctor. Exercise great care when switching from one type of insulin
to another. Each type of insulin has a different colour and symbol on the packaging and cartridge to help you
easily distinguish between them.

2. What you need to know before using Humulin I

Humulin I in cartridges is suitable only for subcutaneous injections with a reusable pen.
Talk to your doctor if you need to inject insulin by another method.
Do not use Humulin I

• If you suspect you are experiencing hypoglycaemia (low blood sugar). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section A in paragraph 4).
• If you are allergic to human insulin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Humulin I.

• If your blood glucose level is well controlled by your current insulin therapy, you may not notice the warning symptoms when your blood sugar is dropping too low. The warning signs are listed later in this leaflet. You must pay careful attention to meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar levels closely, measuring them frequently.
• Some people who experienced hypoglycaemia (low blood sugar) after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less obvious or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist, or nurse at the diabetes centre.
• Have you been ill recently?
• Do you have liver or kidney problems?
• Are you doing more physical exercise than usual?
• Your insulin requirements may change if you consume alcohol.
• Also inform your doctor, pharmacist, or nurse at the diabetes centre if you are planning to travel abroad. Time zone differences between countries may require changes in the timing of your insulin injections and meals compared to your usual routine at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of stroke who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (oedema).

Skin changes at the injection site:
Rotate your injection sites 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 Humulin I"). If you are currently injecting 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.

For athletes: Using this medicine without a therapeutic need constitutes doping and may lead to a positive anti-doping test.

Other medicines and Humulin I
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Your insulin requirements may change if you are taking:

• glucocorticoids
• thyroid hormone replacement therapy
• oral hypoglycaemics (antidiabetic medicines)
• acetylsalicylic acid (aspirin)
• growth hormone
• octreotide, lanreotide
• beta-stimulants (e.g., ritodrine, salbutamol, terbutaline)
• beta-blockers
• thiazides and certain antidepressants (monoamine oxidase inhibitors)
• danazol
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril) or angiotensin II receptor antagonists.

Pregnancy, breastfeeding and fertility
Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet.
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines
Your ability to concentrate and react may be reduced if you experience a hypoglycaemic reaction (low blood sugar). Be aware of this potential problem in any situation where you could put yourself or others at risk (e.g., driving a vehicle or operating machinery). You should consult your diabetes nurse or doctor about whether it is safe for you to drive if you have:

• frequent episodes of hypoglycaemia
• reduced or absent warning signs of hypoglycaemia

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

3. How to use Humulin I

The 3 ml cartridge must only be used with 3 ml pens. Do not use with 1.5 ml pens.
Always check the packaging and the label of the cartridge for the name and type of insulin
supplied to you by the pharmacist. Make sure that the Humulin package corresponds to the one
prescribed by your doctor.
Always use this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist. To prevent the possible transmission of diseases,
each cartridge must be used only by you, even if the needle attached to the delivery device is changed.

Dosage

• Normally, you should inject Humulin I as basal insulin. Follow your doctor's instructions exactly regarding the amount, timing, and frequency of administration; these instructions are intended specifically for you. Follow them precisely and have your condition monitored regularly at a diabetes clinic.
• If you change the type of insulin you are using (for example, from animal insulin to human insulin), you may need a different dose (higher or lower) than before. This change may occur with the first injection, or it may be adjusted gradually over several weeks or months.
• Humulin I in cartridges is suitable only for subcutaneous injection using a reusable insulin pen. Talk to your doctor if you need to administer insulin by another method.

Preparation of Humulin I

• Immediately before use, cartridges containing Humulin I must be rolled 10 times between the palms of the hands and inverted 180° for 10 times to resuspend the insulin until it appears uniformly cloudy or milky. If this does not occur, repeat the procedure until the components are fully mixed. The cartridges contain a small glass bead that facilitates mixing. Do not shake vigorously, as this may cause foaming, which could impair accurate dose measurement. Cartridges should be inspected frequently and must not be used if floating residues or white particles adhering to the bottom or sides of the cartridge are observed, giving it a frosty appearance. Check this before each injection.

Preparing the pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• You must use Humulin I cartridges only with Lilly insulin pens to ensure correct dose delivery.
• Follow the instructions provided with the pen. Insert the cartridge into the pen.
• Set the dose to 1 or 2 units. Then hold the pen with the attached needle pointing upward and gently tap the side of the pen to allow air bubbles to rise. With the pen still pointing upward, press the injection button until a drop of Humulin I appears at the needle tip. Small air bubbles may remain in the pen; these are not dangerous, but if they are too large, they may affect the accuracy of the dose administered.

Injecting Humulin I

• Before injecting, disinfect the skin as instructed. Inject the medicine subcutaneously as you have been taught. Do not inject directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure each injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.

After injection

• Immediately after completing the injection, remove the needle from the pen using the outer needle cap. This will help keep Humulin I sterile, prevent leakage of the medicine, avoid air entering the pen, and prevent needle blockage. Under no circumstances should you share your needles or your pen with others. Replace the cap on the pen.

Subsequent injections

• Leave the cartridge in the pen. Before each subsequent injection, select 1 or 2 units and press the injection mechanism while holding the pen upright until a drop of Humulin I appears at the needle tip. You can estimate how much Humulin I remains in the cartridge by observing the level on its side. The distance between each line corresponds to approximately 20 units. If there is not enough remaining for the next dose, replace the cartridge.

Do not mix any other insulin into a Humulin I cartridge. Once the cartridge is empty, do not reuse it.

If you use more Humulin I than you should
If you use more Humulin I than prescribed, your blood sugar level may drop.
Check your blood sugar level (see section A in paragraph 4).

If you forget to use Humulin I
If you use less Humulin I than prescribed, your blood sugar level may rise.
Check your blood sugar level. Do not inject a double dose to make up for the missed dose.

If you stop using Humulin I
If you use less Humulin I than prescribed, your blood sugar level may rise.
Do not change the type of insulin unless instructed by your doctor.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Human insulin can cause hypoglycaemia (low blood sugar levels). See further information on hypoglycaemia below, in the subsection “Common problems of diabetes”.

Possible side effects
Systemic allergy is very rare (affects fewer than 1 in 10,000 people). Symptoms include:

• drop in blood pressure
• rash all over the body
• difficulty breathing
• shortness of breath
• rapid heartbeat
• sweating

If you think Humulin I is causing you this type of insulin allergy, inform your doctor immediately.

Local allergy is common (affects fewer than 1 in 10 people). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears within a few days or weeks. If this occurs, inform your doctor.

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 100 people). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency is unknown). Insulin may not work well if injected into an area with lumps. Change your injection site with each injection to prevent these skin changes.

Oedema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving glycaemic control.

Common problems of diabetes

A. Hypoglycaemia
Hypoglycaemia (low blood sugar) means there is not enough sugar in the blood. Hypoglycaemia can be caused by:

• an excessive dose of Humulin I or another insulin;
• delayed or missed meals, or changes in diet;
• excessive physical exercise or work performed shortly before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• changes in insulin requirements;
• worsening of a pre-existing kidney or liver disorder.

Alcohol and certain medicines can interfere with your blood sugar levels.

Usually, the first symptoms of hypoglycaemia appear rapidly and include:

• tiredness
• rapid heartbeat
• nervousness or restlessness
• discomfort
• headache
• cold sweat

If you are unable to recognise the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.

Do not use Humulin I if you think you are experiencing hypoglycaemia (low blood sugar).

If your blood sugar level is low, eat glucose tablets, sugar, or drink a sugary beverage. Then eat fruit, biscuits, or a sandwich as advised by your doctor, and rest. Often this is sufficient to counteract mild hypoglycaemia or a minor insulin overdose. If you notice your condition worsening, with shortness of breath and pale skin, inform your doctor immediately. An injection of glucagon can treat moderately severe hypoglycaemia. Take glucose or sugar after a glucagon injection. If there is no positive response to glucagon, you must be admitted to hospital. Ask your doctor for information on the use of glucagon.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means there is not enough insulin in your body. Hyperglycaemia can be caused by:

• missing a dose of Humulin I or another insulin;
• taking less insulin than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:

• drowsiness
• loss of appetite
• flushed face
• fruity breath odour
• thirst
• feeling unwell

Heavy breathing and rapid pulse are severe symptoms. Seek immediate medical help.

Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, unconsciousness, coma, and even death.

Three simple measures to avoid hypoglycaemia or hyperglycaemia are:

• Always keep spare syringes and a vial of Humulin I available
• Always carry identification indicating that you have diabetes
• Always carry sugar with you

C. Illnesses
If you are ill, especially if you feel unwell or are sick, your insulin requirements may change. Even when you are not eating normally, you still need insulin. Test your urine and blood; when unwell, follow the precautions you already know and inform your diabetes nurse or doctor.

Reporting of side effects
If you get 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. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humulin I

Keep this medicine out of the sight and reach of children.
Before use, store Humulin I in a refrigerator (2°C - 8°C). Do not freeze. During use,
store the pen and cartridge at room temperature (below 30°C) for up to 28 days. Do not store the pen or cartridges you are currently using in the refrigerator. Do not place the product near a heat source or direct sunlight.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of that month.
Do not use this medicine if you notice floating particles or white deposits attached to the bottom or walls of the cartridge, giving it a frosted appearance. Check for these signs before each injection.
Do not dispose of any medicine 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 Humulin I contains

• The active substance is human insulin. Human insulin is produced in the laboratory using a technology called "recombinant DNA". It has the same structure as the natural hormone produced by the pancreas and is therefore different from animal insulins. The human insulin present in Humulin I is suspended together with protamine sulfate.
• The excipients are protamine sulfate, metacresol, phenol, glycerol, disodium phosphate 7H₂O, zinc oxide and water for injections. Sodium hydroxide or hydrochloric acid may have been used during the manufacturing process to adjust the pH.

Description of the appearance of Humulin I and contents of the pack
Humulin I (Isophane) 100 IU/ml injectable suspension is a sterile white suspension containing
100 units of insulin per milliliter (100 IU/ml). Each cartridge contains 300 units (3 milliliters).
Cartridges are available in packs of 5 and 10.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
The marketing authorization is held by Eli Lilly Italia S.p.A., Via Gramsci 731/733, 50019 Sesto Fiorentino (FI), Italy.
Humulin I in cartridges is manufactured by:
Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France
Eli Lilly Italia S.p.A., Via A. Gramsci, 731-733, 50019 Sesto Fiorentino, Italy

This medicinal product is authorized in the European Economic Area countries under the following names:
Huminsulin „Lilly“ Basal (Austria)
Humuline NPH (Belgium, Luxembourg, Netherlands)
Humulin N (Bulgaria, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovenia)
Humulin N (NPH) Cartridge (Czech Republic, Slovakia)
Huminsulin Basal (NPH) für Pen 3 ml (Germany)
Humulin NPH (Cyprus, Greece, Norway, Portugal, Sweden)
Humulin I (Ireland, Italy, Malta, United Kingdom)
Umuline NPH (France)

Package leaflet: Information for the user

HUMULIN 30/70 (Mixture) 100 IU/ml injectable suspension in cartridge

(human insulin)
Please read this leaflet carefully 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 you, because it could be dangerous. If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Humulin 30/70 is and what it is used for
2. What you need to know before using Humulin 30/70
3. How to use Humulin 30/70
4. Possible side effects
5. How to store Humulin 30/70
6. Contents of the pack and other information

1. What Humulin 30/70 is and what it is used for

The active substance in Humulin 30/70 is human insulin, which is used in the treatment of diabetes.
Diabetes is a disease caused by the pancreas not producing enough insulin to adequately control blood
glucose levels. Humulin 30/70 is used to control glucose levels over the long term. It is a premixed
suspension of fast-acting insulin and prolonged-acting insulin. The prolonged action is due to the
presence of protamine sulfate in the suspension.
Your doctor may prescribe Humulin 30/70 or another type of prolonged-acting insulin.
Each type of insulin is packaged with its own patient information leaflet containing instructions for proper
use. Do not switch insulin types unless instructed by your doctor. Be very careful when changing the
type of insulin. Each type of insulin has a different colour and symbol on the packaging and cartridge to
help you easily distinguish the differences.

2. What you need to know before using Humulin 30/70

Humulin 30/70 in cartridges is suitable only for subcutaneous injection using a reusable pen.
Talk to your doctor if you need to inject insulin by another method.
Do not use Humulin 30/70

• If you suspect you are experiencing hypoglycaemia (low blood sugar). Instructions for managing mild hypoglycaemia are provided later in this leaflet (see section A in section 4).
• If you are allergic to human insulin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or diabetes nurse before using Humulin 30/70.

• If your blood glucose level is well controlled by your current insulin therapy, you may not notice the warning signs when your blood sugar level is dropping too low. The warning signs are listed later in this leaflet. You must pay close attention to your meal times, frequency and intensity of physical exercise. You should also monitor your blood sugar levels frequently.
• Some people who experienced hypoglycaemia after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycaemia were less noticeable or different. If you frequently experience hypoglycaemia or have difficulty recognizing it, discuss this with your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist, or diabetes nurse.
• Have you been ill recently?
• Do you have liver or kidney problems?
• Are you doing more physical exercise than usual?
• Your insulin requirement may change if you consume alcohol.
• Also inform your doctor, pharmacist, or diabetes nurse if you are planning to travel abroad. Time zone differences between countries may require adjustments to your insulin injection and meal times compared to your usual routine at home.
• Some patients with long-standing type 2 diabetes and heart disease or a history of stroke who were treated with pioglitazone and insulin have reported developing heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (oedema).

Skin changes at the injection site:
Rotate your injection sites to prevent skin changes such as the formation of lumps under the skin. Insulin may not work as effectively if injected into an area with lumps (see section "How to use Humulin 30/70"). If you are currently injecting 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 adjust your insulin dose or other antidiabetic medications.

For athletes: The use of this medicine without a therapeutic need constitutes doping and may lead to a positive anti-doping test.

Other medicines and Humulin 30/70
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Your insulin requirements may change if you are taking:

• glucocorticoids
• thyroid hormone replacement therapy
• oral hypoglycaemics (antidiabetic medicines)
• acetylsalicylic acid (aspirin)
• growth hormone
• octreotide, lanreotide
• beta-stimulants (e.g., ritodrine, salbutamol, terbutaline)
• beta-blockers
• thiazides and certain antidepressants (monoamine oxidase inhibitors)
• danazol
• certain angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril) or angiotensin II receptor antagonists.

Pregnancy, breastfeeding, and fertility
Insulin requirements generally decrease during the first trimester of pregnancy and increase during the following six months. If you are breastfeeding, you may need to adjust your insulin dose or diet.
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines
Your ability to concentrate and react may be reduced if you experience a hypoglycaemic reaction (low blood sugar). Be aware of this potential problem in any situation where you could place yourself or others at risk (e.g., driving a vehicle or operating machinery). Consult your diabetes nurse or doctor about whether it is safe for you to drive if you have:

• frequent episodes of hypoglycaemia
• reduced or absent warning signs of hypoglycaemia

Humulin 30/70 contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Humulin 30/70

The 3 ml cartridge must only be used with 3 ml pens. Do not use with 1.5 ml pens.
Always check the package and the label of the cartridge for the name and type of insulin dispensed to you by the pharmacist. Make sure that the Humulin package corresponds to the one prescribed by your doctor.
Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. To prevent the possible transmission of diseases, each cartridge must be used by you alone, even if the needle on the delivery device is changed.

Dosage

• Follow your doctor’s instructions exactly regarding dose amount, timing, and frequency of administration—these instructions are intended solely for you. Follow them precisely and have your condition monitored regularly at a diabetes care center.
• If you change the type of insulin you are using (for example, from animal insulin to human insulin), you may need a different dose (higher or lower) than before. This change may occur with the first injection, or it may be adjusted gradually over several weeks or months.
• Humulin 30/70 in cartridges is intended only for subcutaneous injection using a reusable insulin pen. Speak with your doctor if you need to administer insulin by another method.

Preparation of Humulin 30/70

• Immediately before use, rotate the cartridges containing Humulin 30/70 ten times between the palms of your hands and then invert them 180° ten times to resuspend the insulin until the solution appears uniformly cloudy or milky. If this does not occur, repeat the procedure until the components are fully mixed. The cartridges contain a small glass bead to aid in mixing. Do not shake vigorously, as this may cause foaming, which could impair accurate dose measurement. Examine the cartridges frequently and do not use them if floating residues or white particles adhering to the bottom or sides of the cartridge are observed, as these may give the cartridge a frosted appearance. Check for this before each injection.

Preparing the pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• You must use Humulin 30/70 cartridges only with Lilly insulin pens to ensure accurate dose delivery.
• Follow the instructions provided with the pen. Insert the cartridge into the pen.
• Set the dose to 1 or 2 units. Then hold the pen with the attached needle pointing upward and tap the side of the pen gently to move air bubbles toward the top. While keeping the pen pointed upward, press the injection button until a drop of Humulin 30/70 appears at the needle tip. Small air bubbles may remain in the pen; these are not dangerous, but if they are too large, they may affect the accuracy of the dose.

Injecting Humulin 30/70

• Before injecting, disinfect the skin as instructed. Inject the medicine subcutaneously as you have been taught. Do not inject directly into a vein. After injection, leave the needle in the skin for 5 seconds to ensure the full dose has been delivered. Do not rub the injection site. Make sure each injection site is at least one centimeter away from the previous one, and remember to rotate injection sites as instructed.

After injection

• Immediately after completing the injection, remove the needle from the pen using the outer needle cap. This step helps maintain the sterility of Humulin 30/70, prevents leakage of the medicine, avoids air entering the pen, and helps prevent needle blockage. Under no circumstances should you share your needles or your pen with others. Replace the cap on the pen.

Subsequent injections

• Leave the cartridge in the pen. Before each subsequent injection, select 1 or 2 units and press the injection mechanism while holding the pen upward until a drop of Humulin 30/70 appears at the needle tip. You can estimate how much Humulin 30/70 remains in the cartridge by observing the level on its side. The distance between each mark corresponds to approximately 20 units. If there is not enough insulin left for the next dose, replace the cartridge.

Do not mix any other insulin into a Humulin 30/70 cartridge. Once the cartridge is empty, do not reuse it.
If you use more Humulin 30/70 than you should
If you use more Humulin 30/70 than prescribed, your blood sugar level may drop. Check your blood sugar level (see section 4, point A).
If you forget to use Humulin 30/70
If you use less Humulin 30/70 than prescribed, your blood sugar level may rise. Check your blood sugar level. Do not inject a double dose to make up for a missed dose.
If you stop using Humulin 30/70
If you use less Humulin 30/70 than prescribed, your blood sugar level may rise. Do not change the type of insulin unless instructed by your doctor.
If you have any doubts about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Human insulin may cause hypoglycaemia (low blood sugar level). See further information on hypoglycaemia below, in the subsection “Common problems of diabetes”.

Possible side effects

Systemic allergy is very rare (affects fewer than 1 in 10,000 people). Symptoms include:

• low blood pressure
• skin rash all over the body
• difficulty breathing
• shortness of breath
• rapid heartbeat
• sweating

If you think Humulin 30/70 is causing you this type of insulin allergy, contact your doctor immediately.

Local allergy is common (affects fewer than 1 in 10 people). In some people, the skin at the injection site may become red, swollen, and itchy. This reaction usually disappears after a few days or weeks. If this occurs, inform your doctor.

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 100 people). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency is not known). Insulin may not work well if you inject into an area with lumps. Change your injection site with each injection to prevent these skin changes.

Oedema (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the beginning of insulin therapy or during changes in therapy aimed at improving glycaemic control.

Common problems of diabetes

A. Hypoglycaemia
Hypoglycaemia (low blood sugar level) means that there is not enough sugar in the blood. Hypoglycaemia may be caused by:

• taking too high a dose of Humulin 30/70 or another insulin;
• delaying or missing a meal, or changing your diet;
• excessive physical exercise or work done immediately before or after a meal;
• an infection or other illness (especially diarrhoea or vomiting);
• changes in insulin requirements;
• worsening of pre-existing kidney or liver disease.

Alcohol and certain medicines can interfere with your blood sugar level.
Usually, the first symptoms of hypoglycaemia appear rapidly and include:

• tiredness
• rapid heartbeat
• nervousness or restlessness
• feeling unwell
• headache
• cold sweat

If you are unable to recognize the warning signs of hypoglycaemia, avoid situations—such as driving a vehicle—where hypoglycaemia could put you or others at risk.
Do not use Humulin 30/70 if you think you are experiencing hypoglycaemia (low blood sugar level).
If your blood sugar level is low, eat glucose tablets, sugar, or drink a sugary drink. Then eat fruit, biscuits, or a sandwich, as your doctor has advised, and rest. Often this is sufficient to counteract mild hypoglycaemia or a minor insulin overdose. If you notice that your condition worsens and you develop shortness of breath and pale skin, contact your doctor immediately. An injection of glucagon can treat moderately severe hypoglycaemia. Take glucose or sugar after a glucagon injection. If you do not respond to glucagon, you must be admitted to hospital. Ask your doctor for information about the use of glucagon.

B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too much sugar in the blood) means that there is not enough insulin in your body. Hyperglycaemia may be caused by:

• missing a dose of Humulin 30/70 or another insulin;
• taking a lower insulin dose than prescribed by your doctor;
• eating much more food than allowed by your diet;
• fever, infection, or severe emotional stress.

Hyperglycaemia can lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. They include:

• drowsiness
• loss of appetite
• flushed face
• fruity-smelling breath
• thirst
• feeling unwell

Heavy breathing and rapid pulse are severe symptoms. Seek medical help immediately.

Untreated hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can become very serious and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death.

Three simple measures to avoid hypoglycaemia or hyperglycaemia are:

• Always keep spare syringes and a vial of Humulin 30/70 available
• Always carry identification indicating that you are diabetic
• Always carry sugar with you

C. Illness
If you are ill, especially if you feel unwell or are sick, your insulin requirements may vary. Even when you are not eating normally, you still need insulin. Test your urine and blood; when unwell, follow the precautions you already know and contact your diabetes nurse or doctor.

Reporting of side effects
If you get 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. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humulin 30/70

Keep this medicine out of the sight and reach of children.
Before use, store Humulin 30/70 in the refrigerator (2°C - 8°C). Do not freeze. During use,
store the pen and cartridge at room temperature (below 30°C) for up to 28 days. Do not store the pen and cartridges you are currently using in the refrigerator. Do not place the product near a heat source or direct sunlight.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of that month.
Do not use this medicine if you notice floating particles or white particles attached to the bottom or sides of the cartridge, which give it a frosted appearance. Check for these signs before each injection.
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 Humulin 30/70 contains

• The active substance is human insulin. Human insulin is produced in the laboratory using a technology called "recombinant DNA technology". It has the same structure as the natural hormone produced by the pancreas. Therefore, it differs from animal insulins. Humulin 30/70 is a premixed suspension containing 30% soluble insulin and 70% insulin with protamine sulfate.
• The excipients are protamine sulfate, metacresol, phenol, glycerol, disodium phosphate 7H₂O, zinc oxide, and water for injections. Sodium hydroxide or hydrochloric acid may have been used during the manufacturing process to adjust the pH.

Description of the appearance of Humulin 30/70 and contents of the pack
Humulin 30/70 (Mixture) 100 IU/ml injectable suspension is a sterile white suspension and contains
100 units of insulin per millilitre (100 IU/ml). Each cartridge contains 300 units (3 millilitres).
Cartridges are available in packs of 5 and 10.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
The marketing authorisation is held by Eli Lilly Italia S.p.A., Via Gramsci 731/733, 50019 Sesto Fiorentino (FI), Italy.
Humulin 30/70 in cartridges is manufactured by:
Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France
Eli Lilly Italia S.p.A., Via A. Gramsci, 731-733, 50019 Sesto Fiorentino, Italy

This medicinal product is authorised in the European Economic Area countries under the following names:
Huminsulin „Lilly“ Profil III 100 I.E./ml (Austria)
Humuline 30/70 (Belgium, Luxembourg, Netherlands)
Huminsulin Profil III für Pen 3 ml (Germany)
Humulin M3 (Bulgaria, Croatia, Cyprus, Ireland, Lithuania, Malta, Portugal, Romania, Slovenia, United Kingdom)
Humulin 30/70 (Italy)
Umuline profil 30 (France)
Humulin M3 (30/70) (Greece, Hungary, Poland)
Humulin M3 (30/70) Cartridge (Czech Republic, Slovakia)