NIULIVA 250 IU/ml SOLUTION FOR INFUSION

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Niuliva 250U.I./ml solution for infusion

Human hepatitis B immunoglobulin

Read all of this leaflet carefully before you start using this medicine.

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

Contents of the pack:

1. What is Niuliva and what is it used for
2. Before you use Niuliva
   1. How to use Niuliva
   2. Possible side effects
   3. Storage of Niuliva

1. Further information

1. What is Niuliva and what is it used for

Niuliva is presented as a solution for intravenous infusion containing 250 U.I./ml of human hepatitis B immunoglobulin.

This medicinal product belongs to the pharmacotherapeutic group called immune sera and immunoglobulins.

Niuliva is used for:

Prevention of hepatitis B virus (HBV) reinfection after liver transplantation due to liver failure caused by hepatitis B in patients without active viral replication before transplantation.

Hepatitis B immunoprophylaxis

• In case of accidental exposure in non-immunized subjects (including individuals with incomplete or unknown vaccination).

• In patients undergoing hemodialysis, until vaccination becomes effective.

• In newborns of mothers carrying the hepatitis B virus.

• In subjects who did not develop an immune response (unmeasurable anti-hepatitis B antibodies) after vaccination and require continuous prevention due to ongoing risk of hepatitis B infection.

If you have any doubts about the use of Niuliva, consult your doctor.

2. Before using Niuliva

Do not use Niuliva

• if you are allergic (hypersensitive) to human immunoglobulins or to any of the other components of Niuliva.

• if you have intolerance to fructose, a rare genetic disease characterized by the inability to break down fructose.

(See special warnings about excipients at the end of this section).

Take special care with Niuliva

Some adverse reactions may occur more frequently

? in the case of high infusion rate.

? if you have hypo- or agammaglobulinemia (a condition characterized by low levels of immunoglobulin in your blood) with or without IgA deficiency.

Pulmonary adverse reactions (acute transfusion-related lung injury, TRALI) may occur if you receive intravenous immunoglobulin.

True hypersensitivity reactions are rare. The symptoms of hypersensitivity reactions are: skin rash, generalized urticaria, chest tightness, difficulty breathing, decreased blood pressure (hypotension), and severe allergic reaction (anaphylaxis).

Niuliva contains a small amount of IgA. If you have IgA deficiency, you are at risk of developing anti-IgA antibodies and suffering allergic reactions after administration of blood-derived products (hemoderivatives) containing IgA. Your doctor should weigh the benefits of treatment with Niuliva against the potential risks of hypersensitivity reactions.

Rarely, human hepatitis B immunoglobulin may induce a drop in blood pressure with an allergic reaction, even if you have previously tolerated treatment with immunoglobulin.

Patients with pre-existing risk factors

Please inform your doctor if you have any other medical condition or disease, as this may require greater caution. In particular, inform your doctor if you have thrombotic risk factors (risk of developing blood clots or thrombi in your circulation).

Consult your doctor, even if any of the above circumstances have occurred to you in the past.

Special safety precautions

When administering medicines derived from human plasma or blood, certain measures must be taken to prevent infections from being transmitted to patients. These measures include careful selection of donors to exclude those at risk of carrying infectious diseases, analysis of specific infection markers in individual donations and plasma pools, as well as inclusion of stages in the manufacturing process to eliminate/inactivate viruses. Despite this, when administering medicines derived from human blood or plasma, the possibility of transmitting infectious agents cannot be entirely excluded. This also applies to emerging or unknown viruses or other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for the non-enveloped hepatitis A virus. The measures taken may have limited value for non-enveloped viruses such as parvovirus B19.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections contained in the product are protective.

It is highly recommended that each time you receive a dose of Niuliva, the name of the medicine and batch number administered be recorded to maintain a record of the batches used.

Use of other medicines

? Inform your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

? Effects on vaccines: Niuliva may reduce the effectiveness of certain types of vaccines such as measles, rubella, mumps, and varicella.

Effects on blood tests

If a blood test is performed after receiving Niuliva, please inform the analyst or your doctor that you have received this medicine. The level of some antibodies may increase.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medicine.

Inform your doctor if you are pregnant or breastfeeding. Your doctor will decide whether Niuliva can be used during pregnancy and breastfeeding.

Driving and using machines

No effects on the ability to drive vehicles or use machinery have been observed.

Important information about some of the components of Niuliva

This medicine contains 50mg of sorbitol per ml.If your doctor has informed you that you suffer from intolerance to some sugars, contact them before using this medicine.

In newborns and children up tothe weaning period, hereditary fructose intolerancemay not have been diagnosed yet, and administration of Niuliva may trigger severe effects. When treatment with Niuliva is considered appropriate for newborns and children (especiallyup to the weaning period), it should be exercised with great caution before and during administration of Niuliva due to the amount of sorbitol contained in the product. This is especially important when more than one dose is needed to achieve protective antibody titers.

No interference with blood glucose level determination is expected.

3. How to use Niuliva

Follow these instructions unless your doctor has given you different instructions.

Prevention of hepatitis B virus (HBV) reinfection after liver transplantation due to liver failure caused by hepatitis B in patients without active viral replication before transplantation:

In adults:

10,000 U.I. on the day of transplantation, during surgery. Afterward, 2,000 - 10,000 U.I./day for 7 days, and as needed to maintain antibody levels above 100 - 150 U.I./l in HBV DNA-negative patients.

In children:

The dosage should be adjusted based on body surface area, at 10,000 U.I./1.73 m2.

Hepatitis B immunoprophylaxis:

• Prevention of hepatitis B in case of accidental exposure in non-immunized subjects:

At least 500 U.I., depending on the intensity of exposure, as soon as possible after exposure, and preferably between 24 - 72 hours.

• Hepatitis B immunoprophylaxis in patients undergoing hemodialysis:

8 - 12 U.I./kg with a maximum of 500 U.I., every 2 months until seroconversion after vaccination.

• Prevention of hepatitis B in newborns of mothers carrying the hepatitis B virus, at birth or as soon as possible after birth:

30 - 100 U.I./kg. Administration of hepatitis B immunoglobulin should be repeated until seroconversion after vaccination.

In all these situations, vaccination against hepatitis B virus is strongly recommended. The first dose of the vaccine can be administered on the same day as the human hepatitis B immunoglobulin, although at different sites.

In subjects who did not develop an immune response (unmeasurable anti-hepatitis B antibodies) after vaccination and require continuous prevention, administration of 500 U.I. in adults and 8 U.I./kg in children every 2 months may be considered; the minimum protective antibody titer is considered 10 mU.I./ml.

Niuliva should be administered intravenously at an initial infusion rate of up to 0.02 ml/kg/min for the first 10 minutes. If you tolerate this infusion rate well, your doctor may gradually increase the infusion rate up to a maximum of 0.04 ml/kg/min. Therefore, generally, administration of 5,000 U.I. will take less than 15 minutes.

If no adverse reactions occur, the initial infusion rate for subsequent infusions will also be up to 0.02 ml/kg/min, and if you tolerate this infusion rate well, your doctor may gradually increase the infusion rate up to a maximum of 0.1 ml/kg/min. In general, the administration time for 5,000 U.I. will be less than 10 minutes.

Niuliva should not be mixed with other medicines or intravenous solutions and should be administered using equipment exclusively for its administration.

If you use more Niuliva than you should

If you have been given more Niuliva than you should, consult your doctor or pharmacist immediately.

The consequences of an overdose are not known.

If you forget to use Niuliva

Consult your doctor or pharmacist immediately and follow their instructions.

You should not be given a double dose to make up for forgotten doses.

4. Possible side effects

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

Tell your doctor if you suffer from any of the following side effects during or after infusion:

? Chills

? Headache

? Fever

? Nausea

? Vomiting

? Allergic reaction

? Joint pain

? Decreased blood pressure (hypotension)

? Mild back pain

Rare side effects:

? Sudden drop in blood pressure and, in isolated cases, anaphylactic shock, even if you have not suffered allergic reactions (hypersensitivity) in previous administrations.

? Cases of temporary inflammation of the meninges (reversible aseptic meningitis).

? Cases of temporary reduction in the number of certain blood cells (hemolytic anemia/reversible hemolysis).

? Cases of transient skin reactions.

? Increases in serum creatinine levels and/or acute renal failure.

Very rare side effects:

? Formation of blood clots in the veins (thromboembolic reactions) that can result in sudden lack of blood supply to the heart muscle (myocardial infarction), stroke, pulmonary defects (pulmonary embolism), or severe obstruction of the veins (deep vein thrombosis).

In two clinical studies conducted with Niuliva, the following side effects were observed:

Uncommon (may affect up to 1 in 100 people):

• Decrease in white blood cells
• Transplant rejection
• Hypokinesia
• Hypotension, hypertension
• Dry mouth
• Joint pain
• Renal failure, acute kidney injury
• Increased liver enzymes, positive throat culture

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Niuliva

Keep out of the reach and sight of children.

Do not use Niuliva after the expiration date stated on the packaging after EXP. The expiration date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C). Do not freeze.

It should be brought to room temperature or body temperature before use.

The solution should be clear or slightly opalescent. Do not use Niuliva if you notice that the solution is cloudy or contains sediment.

Disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Further information

Composition of Niuliva

The active substance is:

Human hepatitis B immunoglobulin. One milliliter of Niuliva contains 50 mg of protein, of which at least 97% is IgG.

The content of human hepatitis B immunoglobulin is 250 U.I./ml (600 U.I./2.4 ml, 1,000 U.I./4 ml, 5,000 U.I./20 ml, and 10,000 U.I./40 ml).

The percentage of IgG subclasses, determined by immunonephelometry, is approximately 74.3% IgG1, 22.1% IgG2, 1.99% IgG3, and 1.61% IgG4.

It contains traces of IgA (less than 0.05 mg/ml).

The other components are sorbitol and water for injectable preparations.

(See section 2, "Before using Niuliva," for more information on components).

Appearance of the product and packaging contents

Niuliva is a solution for infusion. The solution is clear or slightly opalescent, colorless or pale yellow.

Presentation:

Niuliva

Syringes of 600 U.I./2.4 ml and 1,000 U.I./4 ml.

Vials of 5,000 U.I./20 ml and 10,000 U.I./40 ml.

Package size: 1 syringe or 1 vial.

Marketing authorization holder and manufacturer

Instituto Grifols, S.A.

Can Guasch, 2 - Parets del Vallès

08150 Barcelona - SPAIN

Date of last revision of this leaflet:January 2018.

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