Kedhbs

Package leaflet: Information for the user

KEDHBs 180 UI/ml Solution for injection, 540 UI/3 ml Solution for injection, 1000 UI/3 ml Solution for injection

Human hepatitis B immunoglobulin
Please read this leaflet carefully before 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 give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What KEDHBs is and what it is used for

KEDHBs is a solution of human specific anti-hepatitis B immunoglobulins, which are antibodies directed against the hepatitis B virus.
KEDHBs 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, thus preventing hepatitis B in the following cases:

• following accidental exposure in non-immunized individuals (i.e. individuals who have not been vaccinated against the hepatitis B virus, including those who have not been fully vaccinated or whose vaccination status is unknown);
• in patients undergoing haemodialysis (i.e. patients with severe renal failure requiring blood purification through an artificial kidney), until vaccination becomes effective;
• in newborns of mothers who are carriers of the hepatitis B virus;
• in individuals who have not shown an immune response following vaccination (i.e. individuals 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 KEDHBs

Do not use KEDHBs

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

Your doctor should therefore evaluate the benefit of treatment with KEDHBs against the potential risk of
allergic reactions.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before using KEDHBs.
The person administering KEDHBs must ensure that the product is not injected into a blood vessel, as this
could cause an acute (or severe) circulatory crisis, known as shock.
If you are a carrier of HBsAg, there is no benefit in administering this product.
Hypersensitivity
Severe allergic reactions are rare.
Rarely, hepatitis B immunoglobulins may cause a sudden drop in blood pressure with respiratory problems,
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,
administration must be stopped immediately. In case of shock, your doctor must follow the standard medical
treatment for shock.
If you notice any of the following symptoms: difficulty breathing, pain and swelling in a limb, loss of mobility or sensation in any part of the body (focal neurological deficits), or chest pain, contact your doctor or the nearest hospital immediately, as these may be symptoms of an ongoing thrombotic event.
When medicines are prepared from human blood or plasma, specific measures are taken to prevent transmission of infections to patients.
These measures include:

• careful selection of blood and plasma donors to ensure that potentially infected donors are excluded;
• testing of donations to confirm the absence 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 transmission of infectious agents cannot be completely ruled out. This also applies to emerging or unknown viruses or other types of infectious agents.
The measures adopted are considered effective against lipid-enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and against 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 each time you are administered KEDHBs, 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 about to have a blood test after receiving KEDHBs, inform the nurse or doctor that you have taken this medicine.
KEDHBs 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 KEDHBs
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
KEDHBs must not be mixed with other medicinal products.
Live attenuated virus vaccines
KEDHBs 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 effectiveness of these vaccines for a period of at least 3 months.
At least three months must elapse after administration of KEDHBs before vaccination with live attenuated virus vaccines.
Three or four weeks must pass after vaccination with live attenuated virus vaccines before administering hepatitis B immunoglobulins. If administration of hepatitis B immunoglobulins is required within three or four weeks after vaccination, revaccination should be performed three months after administration of the hepatitis B immunoglobulins.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
The safety of 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, the fetus or the newborn are not expected.
Breastfeeding
The safety of using KEDHBs during breastfeeding has not been established in controlled clinical studies and therefore it should be administered with caution in breastfeeding women.
Immunoglobulins are excreted in breast milk and may contribute to protecting the newborn from pathogens entering via mucosal routes.
Fertility
Clinical experience with immunoglobulins suggests that harmful effects on fertility are not expected.
Driving and using machines
KEDHBs does not affect or has negligible effect on the ability to drive and use machines. Patients who experience adverse reactions during treatment should wait until these have resolved before driving or using machines.
KEDHBs 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 and pre-filled syringe (main component of table salt).
This corresponds to 0.19% and 0.58% respectively of the maximum daily dietary intake recommended for an adult.

3. How to use KEDHBs

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
KEDHBs must be administered by intramuscular injection.
The product should be brought to room or body temperature before use.
Vials: Remove the central protection from the rubber stopper and draw the solution into a syringe using an injection needle. Replace the injection needle on the syringe before injecting.
Once the solution has been drawn into the syringe from the container, the medicine must be administered immediately.
Pre-filled syringe: Screw on the plunger rod and inject.
Caution: The injection must be given only after ensuring that a blood vessel has not been entered.
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 for children or > 5 ml for adults), it is recommended to administer them as divided doses at different injection sites.
Furthermore, if you suffer from severe thrombocytopenia or other coagulation disorders, KEDHBs must not be administered by intramuscular injection.

Dosage
Your doctor will determine the appropriate dose for you.
The usual doses are as follows:
For prevention of hepatitis B recurrence after liver transplantation due to liver failure caused by hepatitis B virus:
Adults
2000 IU every 15 days.
For long-term treatment, the dosage should aim to maintain serum levels of anti-HBsAg antibodies above 100 IU/l in HBV-DNA negative patients and above 500 IU/l in HBV-DNA positive patients. This dosage regimen should be adjusted during long-term treatment to ensure maintenance of serum anti-HBsAg antibody levels above 100 IU/l in HBV-DNA negative patients and above 500 IU/l in HBV-DNA positive patients.
Concomitant use of appropriate antiviral agents should be considered, if appropriate, as standard practice in the prophylaxis of hepatitis B reinfection.

Use in children
There are no data available on the use of KEDHBs 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 IU, depending on the extent of exposure, as soon as possible after exposure, preferably within 24–72 hours.
Immunoprophylaxis of hepatitis B in haemodialysis patients:
8–12 IU/kg up to a maximum of 500 IU, every 2 months until vaccination becomes effective.
Prevention of hepatitis B in newborns born to mothers who are carriers of hepatitis B virus, at birth or as soon as possible after birth:
30–100 IU/kg. Repeated administration of hepatitis B immunoglobulins may be necessary until vaccination becomes effective.

In all these situations, hepatitis B vaccination is strongly recommended. The first dose of vaccine and hepatitis B immunoglobulins may be administered on the same day, but at different injection 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 IU (in adults) and 8 IU/kg (in children) every 2 months.

If you use more KEDHBs than you should
The consequences of overdose are not known.

4. Possible side effects

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

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

The following side effects may generally occur after treatment with immunoglobulins administered by intramuscular injection:

• Occasionally, adverse reactions such as tachycardia (accelerated 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 previously shown hypersensitivity to the medicine.
• Local reactions at the injection site: tenderness, swelling, redness (erythema), hardening, local warmth, itching, rash and stinging, may occur frequently.

The following adverse events have been reported following administration of KEDHBs 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
• Chills
• Unusual weakness (asthenia)

For information regarding safety with respect to transmissible agents, see section 2 "What you need to know before using KEDHBs".
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 experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via
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 KEDHBs

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 the medicine 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 KEDHBs and contents of the pack” in section 6). Do not dispose of any medicine 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 pack and other information

What KEDHBs contains
The active substance is human 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.
The excipients are glycine, sodium chloride, water for injections.
Description of the appearance of KEDHBs and contents of the pack
KEDHBs is an injectable solution.
The solution may be colourless or pale yellow or light brown; slight opalescence or a small amount of suspended particles may appear during storage.
KEDHBs “180 IU/1 ml solution for injection” vial containing 180 IU in 1 ml
KEDHBs “540 IU/3 ml solution for injection”: vial containing 540 IU in 3 ml
KEDHBs “1000 IU/3 ml solution for injection”: pre-filled syringe containing 1000 IU in 3 ml
Marketing Authorization Holder and Manufacturer
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 (Naples).
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