Solution for intramuscular injection

Instructions for use of the medicinal product (for patients)

International non-proprietary name: Human Hepatitis B Immunoglobulin

Composition

Active substance:
1 ml of solution contains 100–180 mg of human proteins.

The distribution of IgG subclasses is as follows:

• IgG1 — 63.7%
• IgG2 — 31.8%
• IgG3 — 3.3%
• IgG4 — 1.2%

In addition, the maximum amount of IgA is 300 μg/ml.

It should be noted that these values represent the proportions and/or concentrations of each subclass in the immunoglobulin product.

The immunoglobulin is produced from the plasma of human donors, which is a common source for such products.

Excipients: glycine, sodium chloride, water for injections.

Description

A clear solution ranging from pale yellow to light brown. During storage, the solution may become slightly cloudy and small particles may appear.

Pharmacotherapeutic group

Immunoglobulins.

ATC code: J06BB04.

Pharmacological properties

IMMUNOHBs is a solution containing human hepatitis B immunoglobulin type B with antibodies against hepatitis B virus.

Pharmacodynamics

The corresponding section of the supplied source contains corrupted/unreadable text in the extracted document, so I have not reconstructed or supplemented it.

The readable part states that IMMUNOHBs demonstrated efficacy. In the study, IMMUNOHBs was administered over a period of 6 months at doses ranging from 2,000 to 2,160 IU every 15 days, depending on the package size.

Before each of the 12 administrations, the mean level of measured HBs antibodies exceeded the specified threshold. At a concentration of 180 IU/ml, the mean level was 403 IU/l, while the minimum level was 106 IU/l.

Published data on efficacy and safety in the pediatric population did not demonstrate significant differences compared with adults with the same condition.

Pharmacokinetics

After intramuscular administration, absorption of human hepatitis B immunoglobulin into the bloodstream begins after 2–3 days.

The half-life of human hepatitis B immunoglobulin is approximately 3–4 weeks, although individual variations may occur between patients.

The breakdown of IgG and IgG complexes takes place in the reticuloendothelial system.

Indications for use

IMMUNOHBs is used in the following situations:

• For prevention of recurrent hepatitis B virus infection after liver transplantation associated with liver failure caused by hepatitis B virus.
• For hepatitis B immunoprophylaxis.
• In non-immunized individuals who may have been exposed to the virus, including persons whose vaccination is incomplete or whose vaccination status is unknown.
• In patients undergoing hemodialysis until vaccination becomes effective.
• In newborns born to mothers who are carriers of hepatitis B virus.
• In patients who have failed to develop an adequate immune response after vaccination (very low levels of hepatitis B antibodies) and during subsequent prophylaxis when the risk of hepatitis B infection persists.

Contraindications

Do not use IMMUNOHBs:

• If you are allergic (hypersensitive) to any component of the product.
• If you are allergic (hypersensitive) to human immunoglobulins.
• IMMUNOHBs must not be administered intramuscularly in cases of severe thrombocytopenia or other disorders of hemostasis.
• IMMUNOHBs must not be administered intravenously.

Special warnings and precautions for use

Traceability

To improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.

Because of the risk of shock, make sure that IMMUNOHBs does not enter a blood vessel.

If the recipient is an HBsAg carrier, administration of this product will not provide any benefit.

Hypersensitivity reactions

True severe hypersensitivity reactions are rare.

IMMUNOHBs contains a small amount of IgA. Individuals with IgA deficiency may develop antibodies against IgA, and anaphylactic reactions may occur following administration of blood components containing IgA. Therefore, when prescribing IMMUNOHBs, the benefits of treatment should be weighed against the potential risk of hypersensitivity reactions.

In rare cases, hepatitis B immunoglobulin may cause anaphylactic shock, even in patients who have previously tolerated human immunoglobulin treatment well.

If an allergic or anaphylactic reaction is suspected, the injection must be stopped immediately. If shock occurs, standard medical treatment for shock should be administered.

Thromboembolism

Although thromboembolic events have not been observed, caution should be exercised in patients with pre-existing risk factors.

Patients should receive an adequate amount of fluids before receiving immunoglobulins.

Particular caution is required in patients with risk factors such as:

• hypertension;
• diabetes mellitus;
• a history of vascular disease or thrombotic episodes;
• acquired or hereditary thrombophilic disorders;
• prolonged immobilization;
• severe hypovolemia;
• disorders that increase blood viscosity.

Patients should be informed about the initial symptoms of thromboembolism, including shortness of breath, pain and swelling of the limbs, focal neurological deficits and chest pain. They should be advised to contact their physician immediately if such symptoms occur.

Transmission of infectious agents

Standard measures for preventing infections resulting from the use of medicinal products prepared from human blood or plasma include:

• selection of donors;
• testing of individual donations and plasma pools for infection markers;
• effective virus inactivation/removal procedures during manufacturing.

Despite these measures, the possibility of transmission of infectious agents cannot be completely excluded when medicinal products prepared from human blood or plasma are administered.

These measures are considered effective against enveloped viruses such as HIV, HBV and HCV, as well as non-enveloped viruses such as HAV.

The measures may have limited effectiveness against non-enveloped viruses such as parvovirus B19.

Clinical experience regarding the unsuccessful transmission of hepatitis A virus and parvovirus B19 through immunoglobulins has been accumulated, and it is also recognized that the antibody content itself contributes positively to viral safety.

It is strongly recommended that whenever IMMUNOHBs is administered to a patient, the product name and batch number should be recorded to maintain a link between the patient and the commercial batch of the product.

Important information about some ingredients of IMMUNOHBs

Each 1 ml of this medicinal product contains 3.9 mg of sodium.

A 3 ml vial contains up to 11.7 mg of sodium, corresponding to approximately 0.19% and 0.58% of the maximum daily sodium intake of 2 g recommended by the WHO for adults, according to the source text.

Interaction with serological tests

Following immunoglobulin injection, the levels of various antibodies passively transferred with human blood may temporarily increase. This may lead to false-positive results in serological tests.

Passively transferred antibodies against erythrocyte antigens, such as A, B and D, may interfere with serological tests for red blood cell antibodies, including the antiglobulin test (Coombs test).

No special precautions are required in the pediatric population.

Interaction with other medicinal products

Tell your doctor if you are currently taking or have recently taken any medicinal products, including medicines obtained without a prescription.

Concomitant use of IMMUNOHBs with live attenuated vaccines

Administration of immunoglobulin may interfere for a period of 3 months with live attenuated vaccines against:

• measles;
• mumps;
• rubella;
• chickenpox.

After administration of this product, live attenuated vaccines should be administered at least 3 months later.

If administration of human hepatitis B immunoglobulin is necessary within 3–4 weeks after vaccination with a live attenuated vaccine, the immunoglobulin should be administered 3–4 weeks after vaccination, and revaccination should be performed 3 months after administration of human hepatitis B immunoglobulin.

Pregnancy and lactation

Pregnancy

Ask your doctor before taking any medicinal product.

The safety of this product during human pregnancy has not been established in controlled clinical trials.

Clinical experience with immunoglobulins suggests that no harmful effects on the fetus or newborn are expected during pregnancy.

Lactation

The safety of this medicinal product in breastfeeding women has not been established in controlled clinical trials. Therefore, it should be administered to breastfeeding women only with caution.

Immunoglobulins are excreted into breast milk and may contribute to the passive transfer of protective antibodies to the newborn.

Effects on the ability to drive and use machines

No studies have been conducted to evaluate the effect of this medicinal product on the ability to drive vehicles or operate potentially hazardous machinery.

Method of administration and dosage

Always use IMMUNOHBs exactly as prescribed by your doctor. If you are unsure, consult your doctor.

After liver transplantation associated with liver failure caused by hepatitis B virus, for prevention of recurrent hepatitis B virus infection

Adults:
2,000 IU every 15 days.

For long-term treatment, doses should be adjusted according to the level of antibodies against HBsAg:

• more than 100 IU/L in HBV-DNA-negative patients;
• more than 500 IU/L in HBV-DNA-positive patients.

The source text gives these thresholds in the corresponding section.

Children

There are no data regarding efficacy in pediatric patients.

Hepatitis B immunoprophylaxis following possible exposure in non-immunized individuals

Depending on the time of exposure, administer at least 500 IU as soon as possible after the expected time of exposure or within 24–72 hours.

Prevention of hepatitis B in patients undergoing hemodialysis

Until the next vaccination following seroconversion:

8–12 IU/kg every 2 months, with a maximum dose of 500 IU.

Newborns

For prevention of hepatitis B infection in newborns born to mothers who are carriers of hepatitis B virus, administer as soon as possible during or after delivery:

30–100 IU/kg.

Repeated administration of hepatitis B immunoglobulin may be necessary until the next vaccination following seroconversion.

In all these situations, vaccination against hepatitis B virus is strongly recommended.

The first dose of vaccine may be administered on the same day as human hepatitis B immunoglobulin, but at a different injection site.

Patients who do not develop an adequate immune response after vaccination

In patients with very low hepatitis B antibody levels and continued risk of hepatitis B infection, subsequent prophylaxis may be administered:

Adults: 500 IU every 2 months.

Children: 8 IU/kg every 2 months.

A minimum protective antibody titre of 10 mIU/ml should be maintained.

IMMUNOHBs should be administered intramuscularly.

When a large volume is administered — more than 2 ml in children or more than 5 ml in adults — it is recommended that the dose be divided and administered at different injection sites.

If vaccination is required at the same time, the vaccine and immunoglobulin should be administered at different injection sites.

If intramuscular administration is contraindicated because of bleeding disorders and no intravenous medicinal product is available, subcutaneous administration may be considered. However, there are no clinical efficacy data supporting subcutaneous administration.

Instructions for use

IMMUNOHBs must not be mixed with other medicinal products.

Before administration, the product should be brought to room temperature or body temperature.

Vials

Remove the central protective cover from the rubber stopper and withdraw the solution into an injection syringe.

Change the needle and administer the injection.

The solution should be injected immediately after being withdrawn from the container.

Pre-filled syringes

Remove the protective cap and administer the injection.

Important: The injection should only be administered after ensuring that a blood vessel has not been punctured.

Once the container has been opened, the medicinal product should be used immediately.

The solution is clear and ranges from pale yellow to light brown.

Do not use the solution if it is cloudy or contains a precipitate.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Adverse reactions

As with all normal human immunoglobulins administered intramuscularly, the following reactions may occur:

• chills;
• headache;
• dizziness;
• fever;
• vomiting;
• allergic reactions;
• nausea;
• decreased blood pressure;
• moderate back pain.

Rarely, normal human immunoglobulins may cause a sudden decrease in blood pressure and, in some cases, anaphylactic shock, even in patients who did not experience hypersensitivity during previous administration.

Local reactions at the injection site may frequently occur, including:

• swelling;
• pain;
• redness;
• induration;
• local warmth;
• itching;
• bruising;
• rash.

If any adverse reaction becomes serious, or if you experience any adverse reaction not listed here, please inform your doctor.

According to data from clinical trials, there are insufficient reliable data regarding the frequency of adverse reactions.

Summary of adverse reactions by system organ class

The frequencies are classified according to MedDRA terminology: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from available data).

Overdose

There are no data regarding overdose.

Pharmaceutical form

1 ml of solution in a vial.

One vial is packaged in a cardboard box together with an information leaflet.

Storage conditions

Store in a refrigerator at 2–8°C, in the original container and in the original package, protected from light.

Do not freeze.

Once the container has been opened, the medicinal product should be used immediately.

Keep out of the reach of children.

Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicinal products that are no longer required. These measures will help protect the environment.

Shelf life

3 years.

Do not use after the expiry date.

Dispensing conditions

Prescription-only medicine.

Manufacturer

Kedrion S.p.A., Italy
Via Provinciale (Loc. Bolognana), 55027, Gallicano (Lucca), Italy.

S.S. 7 bis Km 19.5, 80029, Sant’Antimo (Napoli), Italy.

CHARLES RIVER LABORATORIES FRANCE – CRLF., France
2109 Route de Chatillon, Romans, 01400, France.

EUROFINS BIOLAB s.r.l., Italy
Via Bruno Buozzi 2, 20055 Vimodrone (MI), Italy.

Registration Certificate Holder

Kedrion S.p.A., Italy
Località Ai Conti, Castelvecchio Pascoli, 55051 Barga, Lucca, Italy