PATIENT INFORMATION LEAFLET

Niuliva 250Human Immunoglobulin for Intravenous Use

Human Anti-Hepatitis B Immunoglobulin

Read this leaflet carefully before you start using the medicine.

-Keep this leaflet, as you may need to read it again.

-Ask your doctor or pharmacist if you have any questions.

-This medicine has been prescribed for you. Do not give it to others, even if they have the same symptoms, as it may harm them.

-If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1.What Niuliva is and what it is used for

2.Before using Niuliva

1. How to use Niuliva
2. Possible side effects
3. Storage of Niuliva

6. Additional information

Niuliva is presented as anintravenous perfusion solution containing 250U.I./ml of human anti-hepatitis B immunoglobulin.

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

Niuliva is used for:

Prevention of re-infection by hepatitis B virus (HBV) after liver transplant due to liver failure caused by hepatitis B in patients without active viral replication pre-transplant.

Immunoprophylaxis of hepatitis B

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

• In patients undergoing hemodialysis, until vaccination becomes effective.

• In newborns of mothers carrying the hepatitis B virus.

• In individuals who did not present an immune response (measurable 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.

No use Niuliva

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

• if you have fructosa intolerance, a rare genetic disorder in which the enzyme responsible for breaking down fructosa is not produced.

(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 rates.

if you have hypogammaglobulinemia (a condition characterized by low levels of immunoglobulins in your blood) with or without IgA deficiency.

Pulmonary reactions (acute lung injury associated with transfusion, TRALI) may occur if you receive intravenous immunoglobulins.

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 may develop anti-IgA antibodies and suffer allergic reactions after administration of products derived from blood (hemoderivatives) that contain IgA.Your doctor must weigh the benefits of treatment with Niuliva against the potential risks of hypersensitivity reactions.

Infrequently, human immunoglobulin anti-hepatitis B may induce a drop in blood pressure with allergic reaction, even if you have previously tolerated treatment with immunoglobulins.

Patients with pre-existing risk factors

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

Consult with your doctor, even if any of the circumstances mentioned above have occurred at any time.

Special safety precautions

When administering medications derived from human plasma or blood, certain measures must be taken to prevent infections from being transmitted to patients. These measures include a careful selection of donors, excluding those at risk of being carriers of infectious diseases, analysis of specific infection markers in individual donations and plasma mixtures, and inclusion of stages in the manufacturing process to eliminate/inactivate viruses. Despite this, when administering medications derived from human blood or plasma, the possibility of transmission of infectious agents cannot be entirely ruled out. 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 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, which are contained in the product, are protective.

It is highly recommended that each time Niuliva is administered, the name of the medication and batch number administered be recorded in order to maintain a record of the batches used.

Use of other medications

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

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 medication. The level of some antibodies may increase.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medication.

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

Driving and operating machinery

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

Important information about some of the components of Niuliva

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

In newborns and children up to the weaning period, hereditary fructosa intolerance may not have been diagnosed yet and the administration of Niuliva may trigger severe effects.When considering treatment for newborns and children (especially up to the weaning period), caution should be exercised before and during the administration of Niuliva due to the amount of sorbitol contained in the product. This is especially important when multiple doses are needed to achieve the protective antibody titre.

No interference is expected in the determination of blood glucose levels.

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

Prevention of hepatitis B virus re-infection after liver transplant due to hepatitis B liver failure in patients without active viral replication pre-transplantin patients without active viral replication pre-transplant:

Adults:

10,000 U.I. on the day of the transplant, during the operation. After 2,000‑10,000U.I./day for 7 days, and as needed to maintain antibody levels above 100‑150U.I./L in patients DNA-VHB negative.

Children:

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

Immunoprophylaxis of hepatitis B:

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

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

• Immunoprophylaxis of hepatitis B in patients on hemodialysis:

8‑12U.I./kg with a maximum of 500U.I., every 2months 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:

30‑100U.I./kg. The administration of hepatitis B immunoglobulin should be repeated until seroconversion after vaccination.

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

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

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

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

Niuliva should not be mixed with other medications or intravenous solutions and should be used with a perfusion equipment exclusively for its administration.

If you use more Niuliva than you should

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

The consequences of an overdose are unknown.

If you forgot to useNiuliva

Consult your doctor or pharmacist immediately and follow their instructions.

Do not administer a double dose to compensate for the missed dose.

Like all medications, Niulivamay cause side effects, although not everyone will experience them.

Inform your doctor if you experience any of the following adverse reactions during or after infusion:

?Chills

?Headache

?Fever

?Nausea

?Vomiting

?Allergic reaction

?Joint pain

?Decreased blood pressure (hypotension)

?Mild back pain

Less common side effects:

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

?Temporary inflammation of the meninges (reversible aseptic meningitis).

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

?Transient skin reactions.

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

Rare side effects:

?Formation of blood clots in veins (thromboembolic reactions) that may result in sudden heart muscle blood supply failure (myocardial infarction), stroke (cerebral infarction), lung defects (pulmonary embolism), or severe vein obstruction (deep vein thrombosis).

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

Less frequent (may affect up to 1 in 100 people):

• Decreased white blood cells
• Transplant rejection
• Hypocinesia
• Hypotension, hypertension
• Dry mouth
• Joint pain
• Renal failure, acute kidney injury
• Increased liver enzyme, positive throat culture

Reporting of 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 the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep out of reach and sight of children.

Do not use Niuliva after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

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

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

The solution must be transparent or slightly opalescent. Do not use Niuliva if you observe that the solution is cloudy or presents sediments.

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations. Medications should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of packaging and unused medicines. In this way, you will help protect the environment.

Composition of Niuliva

The active principle is:

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

The content of human anti-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 injection preparations.

(See section 2. “Before using Niuliva” for more information on components).

Appearance of the product and contents of the package

Niuliva is a perfusion solution. The solution is transparent or slightly opalescent, colorless or pale yellow.

Presentations:

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 responsible manufacturer

Instituto Grifols, S.A.

Can Guasch, 2 - Parets del Vallès

08150 Barcelona - SPAIN

Last review date of this leaflet:January 2018.

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