Niuliva

PATIENT LEAFLET: INFORMATION FOR THE USER

Niuliva 250 IU/ml solution for infusion

Human hepatitis B immunoglobulin
Please read this leaflet carefully before using this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Never give it to others. It could be harmful to other people, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Niuliva is and what it is used for
2. Before you use Niuliva
3. How to use Niuliva
4. Possible side effects
5. How to store Niuliva
6. Further information

1. WHAT NIULIVA IS AND WHAT IT IS USED FOR

Niuliva is an intravenous infusion solution containing 250 IU/ml of human immunoglobulins against hepatitis B.
This medicinal product belongs to the pharmacotherapeutic group known as immune sera and immunoglobulins.
Niuliva is indicated for:
Prevention of hepatitis B virus (HBV) reinfection after liver transplantation due to hepatitis B-related liver failure in patients without active viral replication prior to transplantation.
Hepatitis B immunoprophylaxis

• In case of accidental exposure in non-immunized individuals (including those with incomplete or unknown vaccination status).
• In patients undergoing haemodialysis, until vaccination becomes effective.
• In newborns born to mothers who are carriers of hepatitis B virus.
• In individuals who have not shown an immune response (undetectable anti-HB antibodies) after vaccination, and in those requiring ongoing prevention due to continuous risk of hepatitis B infection.

If you have any questions about the use of Niuliva, ask your doctor.

2. BEFORE USING NIULIVA

Do not use Niuliva

• if you are allergic (hypersensitive) to human immunoglobulins or to any of the excipients of Niuliva.
• if you have hereditary fructose intolerance, a rare genetic disorder in which the enzyme needed to metabolize fructose is absent. (See special warnings on excipients at the end of this section).

Take special care with Niuliva
Adverse reactions may occur more frequently

• if the infusion rate is too high.
• if you have hypo- or agammaglobulinemia (a condition characterized by low levels of immunoglobulins in your blood), with or without IgA deficiency.

Pulmonary adverse reactions (acute transfusion-related lung injury, TRALI) may occur when intravenous immunoglobulins are administered.
True hypersensitivity reactions are rare. Symptoms of hypersensitivity reactions include:
urticaria, generalized hives, chest tightness, wheezing, hypotension, and anaphylaxis.
Niuliva contains a small amount of IgA. If you have IgA deficiency, you are at risk of developing anti-IgA antibodies and may experience anaphylactic reactions after administration of blood products containing IgA. Therefore, your doctor must carefully weigh the benefits of treatment with Niuliva against the potential risk of hypersensitivity reactions.
Rarely, human anti-hepatitis B immunoglobulin may cause a sudden drop in blood pressure with an allergic reaction, even if you previously tolerated immunoglobulin treatment.

Patients with pre-existing risk factors
Inform your doctor if you have any other illness or condition that may be unfavorable, as caution is required. In particular, tell your doctor if you have thrombotic risk factors.
Also inform your doctor if you have previously experienced any of these conditions.

Special warnings
When medicines are manufactured from human plasma or blood, precautionary measures are taken to prevent infections that could be transmitted to patients. These measures include careful selection of plasma and blood donors to ensure that donors at risk of infection are excluded, and testing of each donation and plasma pool for viruses or infections. In addition, manufacturers of these types of medicines include viral inactivation or removal steps in the plasma or blood processing procedure. Despite these measures, when medicines derived from human plasma or blood are administered, the possibility of transmitting infection cannot be completely ruled out. This applies to all viruses of unknown origin, emerging viruses, or other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as against non-enveloped viruses such as hepatitis A virus. However, the effectiveness of these measures may be limited against non-enveloped viruses such as parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, probably because the antibodies against these infections present in the product provide a protective effect.

For your own safety, whenever Niuliva is administered to you, it is recommended that the name and batch number of the product be recorded each time.

Use with other medicines

• Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those not requiring 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 you are due to have blood tests after taking Niuliva, tell the nurse or doctor that you have taken this medicine. Levels of certain antibodies may increase.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
If you are pregnant or breastfeeding, inform your doctor. Your doctor will decide whether Niuliva can be used during pregnancy or breastfeeding.

Driving and using machines
No effects on the ability to drive or operate machinery have been observed.

Important information about certain excipients in Niuliva
This medicine contains 50 mg of sorbitol per ml. If your doctor has told you that you have
an intolerance to certain sugars, consult him/her before taking this medicine.
In newborns and young children up to weaning age, hereditary fructose intolerance may not yet have been diagnosed, and administration of Niuliva may cause severe reactions. When treatment in newborns and young children (especially up to weaning age) is considered appropriate, caution must be exercised before and during administration of Niuliva due to the sorbitol content of the product. This is particularly important when multiple doses are required to achieve protective antibody levels.
No interference with blood glucose measurements is expected.

3. HOW TO USE NIULIVA

Follow these instructions unless your doctor has prescribed otherwise:

Prevention of hepatitis B virus (HBV) reinfection after liver transplantation for hepatitis B-related liver failure in patients without active viral replication prior to transplantation:

In adults:
10,000 IU on the day of transplantation, during the perioperative phase. Subsequently, 2,000 – 10,000 IU/day for 7 days, and as needed to maintain antibody levels above 100 – 150 IU/L in HBV-DNA negative patients.

In children:
Dosage should be adjusted according to body surface area, based on a value of 10,000 IU/1.73 m².

Hepatitis B immunoprophylaxis:

• Prevention of hepatitis B following accidental exposure in non-immunized individuals:
  At least 500 IU, depending on the extent of exposure, as soon as possible after exposure and preferably within 24 – 72 hours.

• Hepatitis B immunoprophylaxis in patients undergoing hemodialysis:
  8 – 12 IU/kg, up to a maximum of 500 IU, every 2 months until seroconversion following vaccination.

• Prevention of hepatitis B in newborns of mothers carrying hepatitis B virus, at birth or immediately after birth:
  30 – 100 IU/kg. Administration of hepatitis B immunoglobulins may be repeated until seroconversion following vaccination.

In all these situations, hepatitis B vaccination is strongly recommended. The first vaccine dose may be administered on the same day as human hepatitis B immunoglobulin, but at different injection sites.

In individuals who have not shown an immune response (undetectable anti-HB antibodies) after vaccination and in those requiring ongoing prevention, administration of 500 IU in adults and 8 IU/kg in children every 2 months may be considered. An antibody titer of 10 mIU/mL is considered the minimum protective level.

Niuliva must be administered intravenously at an initial maximum rate of 0.02 ml/kg/min for the first 10 minutes. If well tolerated, the infusion rate may be gradually increased by the physician up to a maximum of 0.04 ml/kg/min. Therefore, in general, administration of 5,000 IU will be completed in less than 15 minutes.

If no adverse reactions occur, the initial maximum rate for subsequent infusions will always be 0.02 ml/kg/min, and if well tolerated, the infusion rate may be gradually increased by the physician up to a maximum of 0.1 ml/kg/min. In general, administration of 5,000 IU will take less than 10 minutes.

Niuliva must not be mixed with other medicinal products or intravenous fluids and must be administered via a separate intravenous line.

If you use more Niuliva than you should
If you have administered more Niuliva than prescribed, inform your doctor or pharmacist immediately.
The consequences of an overdose are unknown.

If you forget to use Niuliva
Inform your doctor or pharmacist immediately and follow their instructions.
Do not administer a double dose to make up for the missed dose.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Niuliva can cause adverse reactions, although not everyone experiences them.
Inform your doctor if you experience any of the following side effects during or after
the infusion:

• Chills
• Headache
• Fever
• Nausea
• Vomiting
• Allergic reactions
• Arthralgia
• Hypotension
• Moderate lower back pain

Rare adverse reactions:

• Sudden drop in blood pressure and, in isolated cases, anaphylactic shock, even if you did not show hypersensitivity during previous administration
• Cases of transient meningitis (reversible aseptic meningitis)
• Cases of temporary reduction in red blood cells in the blood (reversible hemolytic anemia/hemolysis)
• Cases of temporary skin reactions
• Increase in serum creatinine levels and/or acute renal failure

Very rare adverse reactions:

• Thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis

The following adverse reactions were observed in two clinical studies conducted with Niuliva:
Uncommon (may occur in 1 patient out of 100):

• Reduction in white blood cells
• Transplant rejection
• Hypokinesia
• Hypotension, hypertension
• Dry mouth
• Joint pain
• Renal failure, acute renal failure
• Increase in liver enzymes, positive pharyngeal swab

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. You may also report adverse reactions directly via
http://www.agenziafarmaco.gov.it/it/responsabili . By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE NIULIVA

Keep Niuliva out of the reach and sight of children.
Do not use Niuliva after the expiry date stated on the label and carton after Exp.
The expiry date refers to the last day of the month.
Store in a refrigerator (2 °C - 8 °C). Do not freeze.
The product 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 a deposit.
All unused products or waste materials must be disposed of according to current regulations.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. OTHER INFORMATION

What Niuliva contains
The active substance is:
Human hepatitis B immunoglobulin. One millilitre of Niuliva contains 50 mg of protein, of which
at least 97% consists of IgG.
The content of human hepatitis B immunoglobulin is 250 IU/ml (600 IU/2.4 ml, 1.000 IU/4 ml,
5.000 IU/20 ml, 10.000 IU/40 ml).
The percentage distribution of IgG subclasses, determined by immunonephelometry, is approximately
74.3% IgG\ , 22.1% IgG\ , 1.99% IgG\ , 1.61% IgG\ .
Contains trace amounts of IgA (less than 0.05 mg/ml).
The excipients are sorbitol and water for injections.
(See section 2. “Before you use Niuliva” for further information on excipients).

Description of the appearance of Niuliva and contents of the container
Niuliva is an infusion solution. The solution is clear or slightly opalescent and colourless or pale yellow.

Presentations:
Niuliva
600 IU/2.4 ml and 1.000 IU/4 ml pre-filled syringes.
5.000 IU/20 ml and 10.000 IU/40 ml vials.

Packaging: 1 syringe or 1 vial.

Marketing Authorisation Holder and Manufacturer
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès
08150 Barcelona - SPAIN