Label: Information for the User

HUMULINA NPH 100UI/ml injectable suspension in vial

(Human Insulin)

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

1. What isHumulina NPHand how it is used

2. What you need to know before starting to use Humulina NPH

3. How to useHumulina NPH

4. Possible adverse effects

5. Storage ofHumulina NPH

6. Contents of the package andadditional information

Humulina NPH contains human insulin as its active ingredient, which is used to treat diabetes. You have diabetes if your pancreas does not produce enough insulin to control your blood glucose level (blood sugar). Humulina NPH is used for long-term glucose control. Its action is prolonged due to the inclusion of protamine sulfate in the suspension.

Your doctor may tell you to use Humulina NPH along with a rapid-acting insulin. Each insulin contains its own leaflet that will inform you about this. Do not change your insulin unless your doctor tells you to. Be careful if you change your insulin. Each type of insulin has a different color and symbol on the packaging and vial so that you can easily distinguish them.

No useHumulina NPH:

• If you think you are starting to have hypoglycemia (low blood sugar).More information on how to treat a mild hypoglycemia is provided later in this leaflet (see section 4, subsection A).(see section 4, subsection A).
• If you are allergic to human insulin or to any of the other components of this medicine (listed in section 6).(listed in section 6).

Warnings and precautions

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

• If your blood sugar levels are well controlled with the insulin you are currently using, you may not feel the warning signs when your blood sugar level drops too low. The warning signs are listed later in this leaflet. You should carefully consider when to take meals, how often to exercise and how intensely. You should also carefully control your blood sugar levels by frequently checking your blood glucose.
• Some people who have had hypoglycemia (low blood sugar) after switching from animal insulin to human insulin have reported that the early warning signs were less obvious or different. If you frequently have hypoglycemia or have difficulty recognizing the symptoms, consult your doctor.
• If your answer to any of the following questions is YES, inform your doctor, pharmacist or nurse.
• • Have you been ill recently?
  • Do you have problems with your kidneys or liver?
  • Are you doing more exercise than usual?
• If you consume alcohol, the amount of insulin you need may also change.
• You should also inform your doctor, pharmacist or nurse if you plan to travel abroad. The time difference between countries may mean that your injections and meals need to be taken at different times than when you are at home.
• Some patients with type 2 diabetes who have had heart problems or who have had a previous stroke, treated with pioglitazone and insulin, have experienced the development of heart failure. Inform your doctor as soon as possible if you have signs of heart failure, such as unusual shortness of breath or rapid weight gain or localized swelling (edema).
• Changes in the skin at the injection site:
• The injection site should be rotated to avoid changes in the skin, such as lumps under the skin. Insulin may not work well if injected into a swollen area (see How to use Humulina NPH). Contact your doctor if you are currently injecting into a swollen area, before starting to inject into a different area. Your doctor may advise you to check your blood sugar levels more closely, and to adjust your insulin or your other diabetes medications.

Use of Humulina NPH with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine.

Your insulin needs may change if you are taking any of the following:

• steroids,
• thyroid hormone replacement therapy,
• oral hypoglycemics (oral diabetes medications),
• aspirin,
• growth hormone,
• octreotide,lanreotide,
• beta-2 stimulants (e.g. ritodrine, salbutamol or terbutaline),
• beta-blockers,
• thiazides or some antidepressants (monoamine oxidase inhibitors),
• danazol,
• some angiotensin-converting enzyme inhibitors (ACE inhibitors) (e.g. captopril, enalapril) or angiotensin II receptor blockers.

Pregnancy, breastfeeding and fertility

Your usual insulin needs may decrease during the first three months of pregnancy and increase during the remaining six months. If you are breastfeeding, you may need to adjust your insulin dose or diet.

If you are pregnant or breastfeeding, think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and operating machinery

Your ability to concentrate and react may be reduced if you suffer from hypoglycemia (low blood sugar). Please remember this in all situations where it may be a risk to you or others (e.g. driving a car or operating machinery). You should consult your doctor or nurse about the advisability of driving if you have:

• frequent episodes of hypoglycemia,
• difficulty perceiving the symptoms of hypoglycemia or do not perceive them.

Humulina NPH contains Sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially “sodium-free”.

Always check the name and type of insulin in the vial and label when you receive it from the pharmacy. Make sure you get the Humulin that your doctor has prescribed for you.Humulinthat your doctor has told you to use.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Dosage

• Humulin NPH should be injected as your basal insulin. Your doctor has told you which insulin to use, how much, when, and how often to inject. These instructions are only for you. Follow them exactly and attend your diabetes clinic regularly.
• If you change from one type of insulin to another (for example from animal to human), you may need to use more or less than before. This may be only in the first injection or it may be a gradual change over several weeks or months.
• Inject Humulin NPH under the skin. Do not administer it using any other route of administration. Under no circumstances should Humulin NPH be injected into a vein.

Preparing Humulin NPH

• The vials containing Humulin NPH must be moved several times between the palms of the hands before use, in order to resuspend the insulin until it becomes a uniform turbid or milky appearance.Noshake vigorously to avoid foam formation, as this may interfere with the correct measurement of the dose. The vials should be examined frequently and not used if there are accumulations of material or white solid particles adhered to the bottom or walls of the vial, giving it a frosty appearance. Check it each time you inject.

Injecting Humulin NPH

• First, wash your hands.
• Before injecting, clean the skin as instructed. Clean the rubber stopper of the vial, but do not remove it.
• Use a new and sterile syringe and needle to pierce the rubber stopper and load the amount of Humulin NPH you need. Your doctor or nurse will instruct you on how to do this.Do not share your needles or syringes.
• Inject under the skin, as instructed. Do not inject directly into a vein. After the injection, keep the needle in the skin for 5 seconds to ensure that the entire dose is administered. Do not rub the area where you just injected. Make sure to inject at least 1 centimeter away from where you injected last time and "alternate" the injection sites as instructed.
• Your doctor will tell you if you need to mix Humulin Regular with Humulin NPH. If, for example, you need to inject a mixture, load the syringe with Humulin Regular before doing so with the long-acting insulin. Inject the liquid as soon as you have mixed it. Repeat the same procedure each time you need to inject a mixture. Normally, do not mix Humulin NPH with a mixture of human insulins. Never mix Humulin NPH with insulins produced by other manufacturers or with animal insulins.
• Do not inject Humulin NPH into a vein. Inject Humulin NPH as your doctor or nurse has instructed you.

If you use more Humulin NPH than you should

If you use more Humulin NPH than you should, your blood sugar may decrease.Check your blood sugar (see section 4, subsection A).

In case of overdose or accidental ingestion, consult the Toxicological Information Service. Phone 91 562 04 20.

If you forgot to use Humulin NPH

If you use less Humulin NPH than you should, your blood sugar levels may increase. Check your blood sugar. Do not inject a double dose to compensate for the missed doses.

If you interrupt treatment with Humulin NPH

If you use less Humulin NPH than you should, your blood sugar levels may become too high. Do not change your insulin unless your doctor tells you to.

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

Like all medications, this medication may cause side effects, although not everyone will experience them.

Human insulin may cause hypoglycemia (low blood sugar). See more information about hypoglycemia below in the subsection “Common problems with diabetes”.

Possible side effects

Systemic allergy:is very rare (affects fewer than 1 in 10,000 treated patients). The symptoms are as follows:

If you think you have this type of allergy to insulin with Humulina NPH, inform your doctor immediately.

Local allergy:is common (affects fewer than 1 in 10 treated patients).In some patients, the injection site becomes red, swollen, or itchy. These symptoms usually disappear within a few days or weeks. If this happens, consult your doctor.

Changes in skin at the injection site:

If insulin is injected too frequently in the same area, the fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy) (may affect up to 1 in 100 people). Bumps under the skin may also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis; the frequency of this is unknown). Insulin may not work well if injected in a thickened area. Change the injection site to help prevent these skin changes.

Swelling (e.g., swelling of arms, ankles, fluid retention) has been reported, especially at the start of insulin treatment or during a change in treatment to improve blood sugar control.

Common problems with diabetes

A.Hypoglycemia

Hypoglycemia (low blood sugar) means there is not enough sugar in the blood. This can happen if:

• You use too much Humulina NPH or other insulin;
• You skip or delay meals or change your diet;
• You exercise or work too hard just before or after a meal;
• You have an infection or illness (especially diarrhea or vomiting);
• You have a change in your insulin needs; or
• You have liver or kidney problems that worsen.

Alcohol and some other medications can affect your blood sugar levels.

The first symptoms of low blood sugar usually appear quickly and include the following:

Until you are sure of recognizing the warning signs, avoid situations such as driving a car, as low blood sugar can pose a risk to you or others.

Do not use Humulina NPH if you think you are starting to have low blood sugar.

If your blood sugar is low, take glucose tablets, sugar, or drink a sweetened beverage. Then take something to eat, such as fruit, cookies, or a snack, as your doctor has instructed, and rest. This should help you recover from mild or small insulin overdose hypoglycemia. If it worsens and your breathing is shallow and your skin is pale, inform your doctor immediately. A glucagon injection can treat severe hypoglycemia. Take glucose or sugar after the glucagon injection. If you do not respond to glucagon, go to the hospital. Ask your doctor for information on glucagon.

B.Hyperglycemia and diabetic ketoacidosis

Hyperglycemia (high blood sugar) means your body does not have enough insulin.

Hyperglycemia can be caused by:

• Not taking your Humulina NPH or other insulin;
• Taking less insulin than your doctor has prescribed;
• Eating more than your diet allows; or
• Fever, infection, or emotional stress.

Hyperglycemia can cause diabetic ketoacidosis. The first symptoms begin slowly over several hours or days. The symptoms include the following:

Severe symptoms include rapid breathing and a fast pulse.Seek medical help immediately.

If hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) are not treated, they can be very serious and cause headaches, nausea, vomiting, dehydration, loss of consciousness, coma, or even death.

Three simple steps to avoid hypoglycemia or hyperglycemia are:

• Always have extra syringes and a vial of Humulina NPH.
• Always carry something that identifies you as a diabetic patient.
• Always carry sugar with you.

C.Illness

If you are ill, especially when you have nausea or vomiting, you may vary the amount of insulin you need.You need to continue taking insulin even when you are not eating as you normally do.Perform urine or blood tests, follow the guidelines that have been indicated for you to perform in these cases, and inform your doctor or nurse.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSpanish System for the Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Before first use, store your Humulin NPH in a refrigerator (between 2°C and 8°C).Do not freeze.

You can store your vial “in use” at room temperature (below 30°C) for up to 28 days. Do not leave it near a heat source or in direct sunlight.

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

Do not use this medication if you observe that there are accumulations of material or white solid particles adhered to the bottom or walls of the vial, giving it an appearance similar to frost.Check it every time you inject.

Medications should not be disposed of through drains or in the trash. Deposit the containers and medications you no longer need at the SIGRE point of your pharmacy. Ask your pharmacist how to dispose of the containers and medications you no longer need. In this way, you will help protect the environment.

Composition ofHumulina NPH

• Theactive principleis human insulin. Human insulin is obtained in the laboratoryby “recombinant DNA technology” and has the same structure as the natural hormone produced by the pancreas. Therefore, it is different from animal insulins. Human insulin in Humulina NPH is presented in the form of a suspension along with protamine sulfate.

• Theother componentsare protamine sulfate, metacresol, phenol, glycerol, sodium dihydrogen phosphate 7H2O, zinc oxide, and water for injectable preparations. During manufacturing, sodium hydroxide and/or hydrochloric acid may have been used to adjust the acidity.

Appearance of the product and contents of the Humulina NPH packaging

Humulina NPH 100UI/ml injectable suspension is awhite and sterile suspension, containing 100 units of human insulin in each milliliter (100UI/ml). Each vial contains 1,000 units (10 milliliters).

Humulina NPH 100UI/ml is presented in a 1 vial or 2 vials or in multiple packaging of 5 (5 x 1) vials.

Only some packaging sizes may be commercially available..

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:Lilly S.A., Avda. de la Industria, nº 30. 28108 Alcobendas, Madrid. Spain.

Responsible manufacturer:

• Lilly S.A., Avda. de la Industria nº 30. 28108 Alcobendas, Madrid. Spain.
• Lilly France S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France.

This medicine is authorized in the member states of the European Economic Area with 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)

HumulinaNPH(Spain)

Humulin I(Ireland, Italy, United Kingdom)

Umuline NPH (France)

Last review date of this leaflet: August 2020.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/