Uman Big

Package leaflet: Information for the user

UMAN BIG 180 UI/ml solution for injection

Human hepatitis B immunoglobulin
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 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, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What UMAN BIG is and what it is used for

UMAN BIG is a human anti-hepatitis B immunoglobulin solution. Immunoglobulins are blood proteins and constitute antibodies.
UMAN BIG is used in the following treatments:

• to prevent recurrence of hepatitis B after liver transplantation due to liver failure caused by the hepatitis B virus.
• to provide rapid availability of antibodies against the hepatitis B virus, thereby preventing hepatitis B in the following cases: following accidental exposure in non-immunized individuals (i.e. people who have not been vaccinated against the hepatitis B virus, including those who have not completed the full vaccination cycle or whose vaccination status is unknown); in patients undergoing haemodialysis (i.e. patients with severe renal failure requiring blood purification via an artificial kidney), until vaccination becomes effective; in newborns born to mothers who are carriers of the hepatitis B virus; and in individuals who have not shown an immune response following vaccination (i.e. people in whom vaccination has not been effective) and who require ongoing prevention due to persistent risk of contracting hepatitis B.

2. What you should know before using UMAN BIG

Do not use UMAN BIG

• If you are allergic to human immunoglobulins or to any of the other ingredients of this medicine (listed in section 6).
• If you have a deficiency of immunoglobulin A (IgA), you may develop antibodies against immunoglobulin A in the blood. UMAN BIG contains small amounts of IgA and therefore may cause severe allergic reactions.

Your doctor must therefore evaluate the benefit of treatment with UMAN BIG against the potential risk of allergic reactions.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using UMAN BIG.

The person administering UMAN BIG must ensure that the product is not injected into a blood vessel; this could cause an acute (or severe) circulatory crisis, known as shock.

If you are a carrier of HBsAg, there is no benefit from administering this product.

Severe allergic reactions are rare.

Rarely, hepatitis B immunoglobulins may cause a sudden drop in blood pressure associated with breathing difficulties, fainting, sometimes fever and skin reactions (anaphylactic reaction). This may occur even if you have previously tolerated treatment with immunoglobulins.

If your doctor or the person administering the medicine suspects an allergic or anaphylactic reaction, the injection must be stopped immediately. In case of shock, your doctor must follow standard medical treatment for shock.

If you experience any of the following symptoms: difficulty breathing, pain and swelling in a limb, loss of movement or sensation in part of the body (focal neurological deficits), or chest pain, seek immediate medical attention or contact the nearest hospital, as these may be symptoms of an ongoing thrombotic event.

The product contains 3.9 mg of sodium per ml. This should be taken into account, based on the total amount of product to be administered, if you are on a low-salt diet.

When medicines are prepared from human blood or plasma, specific measures are implemented to prevent transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to ensure that potentially infected individuals are excluded;
• testing of donations to detect the presence of infectious agents and/or viruses;
• inclusion during the manufacturing process of steps capable of inactivating or removing viruses.

Despite these measures, when administering medicines prepared from human blood or plasma, the possibility of transmitting infectious agents cannot be completely ruled out. This applies also to emerging or unknown viruses or other types of infectious agents.

The measures adopted are considered effective against lipid-enveloped viruses such as the human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and the non-lipid-enveloped hepatitis A virus (HAV).

The measures taken may have limited effectiveness against non-lipid-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 contained in the product have protective properties.

It is strongly recommended that every time UMAN BIG is administered to you, the name and batch number of the product are recorded, in order to maintain traceability of the batch used.

Effects on blood tests

If you are due to have a blood test after receiving UMAN BIG, inform the nurse or doctor that you have taken this medicine.

UMAN BIG may interfere with certain tests for red blood cell antibodies.

Children

No specific measures or monitoring are required for the paediatric population.

Other medicines and UMAN BIG

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

UMAN BIG must not be mixed with other medicinal products.

Live attenuated virus vaccines

UMAN BIG may interfere with the development of an immune response to live attenuated virus vaccines, such as those for rubella, mumps, measles, and varicella. Administration of immunoglobulins may alter the efficacy of these vaccines for a period of at least 3 months. At least three months must elapse after administration of UMAN BIG before vaccination with live attenuated virus vaccines.

Three or four weeks must pass after vaccination with live attenuated virus vaccines before administering human hepatitis B immunoglobulins. If administration of human hepatitis B immunoglobulins is required within three or four weeks after vaccination, revaccination should be performed three months after administration of the human hepatitis B immunoglobulins.

Pregnancy, breastfeeding and fertility

If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

The safety of using this medicine during human pregnancy has not been established in controlled clinical studies and therefore it should be administered with caution in pregnant women.

Clinical experience with immunoglobulins suggests that harmful effects on the course of pregnancy or on the fetus and newborn are not expected.

Breastfeeding

The safety of using UMAN BIG during breastfeeding has not been established in controlled clinical studies and therefore it should be administered with caution in women who are breastfeeding.

Immunoglobulins are excreted in breast milk and may help protect the newborn from pathogens entering through mucosal surfaces.

Fertility

Clinical experience with immunoglobulins suggests that harmful effects on fertility are not expected.

Driving and using machines

UMAN BIG does not affect or affects negligibly the ability to drive or use machinery. Patients who experience adverse reactions during treatment should wait until symptoms resolve before driving or using machinery.

UMAN BIG contains sodium

This medicine contains up to a maximum of 3.9 mg of sodium per 1 ml vial and 11.7 mg of sodium per 3 ml vial (main component of table salt).

This corresponds to 0.19% and 0.58% of the recommended maximum daily dietary intake of sodium for an adult, respectively.

3. How to use UMAN BIG

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
UMAN BIG must be administered by intramuscular injection.
The product should be brought to room or body temperature before use.
Remove the central protective cap from the rubber stopper and withdraw the solution using an injection syringe.
Replace the injection needle on the syringe and administer the injection.
Once the solution has been drawn into the syringe from the container, the medicine must be administered immediately.
The solution is clear and colourless or pale yellow or light brown. Do not use solutions that appear cloudy or contain deposits.
If high doses are required (> 2 ml in children or > 5 ml in adults), it is recommended to administer them as divided doses at different injection sites.
Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

Dosage
Your doctor will determine the appropriate dose for you.
The commonly used doses are as follows:

For prevention of hepatitis B recurrence after liver transplantation due to liver failure caused by hepatitis B virus:
Adults
The recommended dosage is 2160 UI i.m. every 15 days during the post-transplant period, excluding the first week. This dosage should be adjusted during long-term treatment to ensure maintenance of serum anti-HBsAg antibody levels above 100 UI/l in HBV-DNA negative patients and above 500 UI/l in HBV-DNA positive patients.
Concomitant use of appropriate antiviral agents should be considered, if appropriate, as standard practice in prophylaxis against hepatitis B reinfection.

Use in children
There are no data available on the use of UMAN BIG in the paediatric population for prophylaxis of hepatitis B infection recurrence after liver transplantation due to liver failure caused by hepatitis B.

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

Immunoprophylaxis of hepatitis B in patients undergoing haemodialysis:
8–12 UI/kg up to a maximum of 500 UI every 2 months, until vaccination becomes effective.

Prevention of hepatitis B in newborns born to hepatitis B virus carrier mothers, at birth or as soon as possible after birth:
30–100 UI/kg. Repeated administration of hepatitis B immunoglobulins may be necessary until vaccination becomes effective.

In all these situations, vaccination against hepatitis B virus is strongly recommended. The first dose of the vaccine and human hepatitis B immunoglobulins may be administered on the same day, but at different sites.

If you have not shown an immune response after vaccination (undetectable anti-hepatitis B antibodies) and ongoing prevention is required, your doctor may consider administering 500 UI (in adults) and 8 UI/kg (in children) every 2 months.

If you use more UMAN BIG than you should
The consequences of overdose with this product are unknown.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following side effects, consult your doctor immediately or contact the nearest
hospital:

• Allergic reactions (hypersensitivity), anaphylactic shock (a severe allergic reaction which may be life-threatening). Symptoms of an allergic reaction/anaphylactic shock include, for example, itching, skin reactions, swelling of the lips, face and tongue, difficulty swallowing, breathing difficulties, fainting.

The following side effects have generally been reported after treatment with immunoglobulins administered intramuscularly:

• Occasionally, adverse reactions such as tachycardia (rapid heartbeat), vasospasm (sudden narrowing of blood vessels), glossitis (swollen tongue), sweating, chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia (joint pain), low blood pressure, and moderate lower back pain may occur.
• Normal human immunoglobulins may rarely cause a sudden drop in blood pressure (hypotension) and, in isolated cases, hypersensitivity reactions (anaphylactic shock), even when the patient has not shown hypersensitivity during previous administrations. Local reactions at the injection site such as pain, swelling, redness (erythema), hardening, local warmth, itching, rash, and stinging may occur frequently. The following side effects have been reported following administration of UMAN BIG after the medicine was placed on the market (frequency cannot be estimated from the available data):
  • Hypersensitivity
• Anaphylactic shock
• Abdominal pain
• Diarrhea
• Vomiting
• Musculoskeletal pain
• Fever
• Malaise
• Unusual weakness (asthenia)

For information regarding safety with respect to transmissible agents, see section 2 "What you need to know before using UMAN BIG".

Additional side effects in children
The frequency, type, and severity of adverse reactions are expected to be the same as in the adult population.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store UMAN BIG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and outer packaging.
The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
Keep in the original outer packaging to protect from light.
Do not freeze.
Do not use this medicine if you notice that the solution is cloudy or contains particles (see also “Description of the appearance of UMAN BIG and contents of the pack” in section 6).
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. Contents of the package and other information

What UMAN BIG contains
The active substance is human anti-hepatitis B immunoglobulins.

Distribution of IgG subclasses:
IgG 63.7%
IgG 31.8%
IgG 3.3%
IgG 1.2%
The maximum IgA content is 300 micrograms/ml.
Produced from plasma of human donors.
Other components are glycine, sodium chloride, water for injections.
Description of the appearance of UMAN BIG and contents of the pack
UMAN BIG is an injectable solution.
The solution may be colorless, pale yellow, or light brown; a slight opalescence or a small amount of suspended particles may appear during storage.
UMAN BIG 180 UI injectable solution: vial containing 180 UI in 1 ml
UMAN BIG 540 UI injectable solution: vial containing 540 UI in 3 ml
Marketing Authorization Holder
Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca).
Manufacturer
Kedrion S.p.A. - S.S. 7 bis Km 19.5, S. Antimo (Napoli).
This medicinal product is authorized in the European Economic Area Member States under the following
names: