Venbig

Human hepatitis B immunoglobulin.

See Table 1.

Click on icon to see table/diagram/image

Distribution of the IgG subclasses: IgG₁ 26.0-40.0 mg/ml.
IgG₂ 13.0-25.0 mg/ml.
IgG₃ 1.20-2.50 mg/ml.
IgG₄ 0.15-0.50 mg/ml.
Maximum IgA content 0.05 mg/ml.
Excipients with known effect: One ml contains 3.565 mg sodium (0.155 mmoles).
One ml contains up to 92 mg sucrose (91.9 mg/ml).
Excipients/Inactive Ingredients: Powder vial: Sucrose, Sodium chloride.
Solvent vial: Sodium chloride, Water for injections.

Pharmacotherapeutic Group: Immune sera and immunoglobulins-Hepatitis B immunoglobulin. ATC Code: J06BB04.
Pharmacology: Pharmacodynamics: Human hepatitis B immunoglobulin contains mainly immunoglobulin G (IgG) with a specifically high content of antibodies against hepatitis B virus surface antigen (HBs).
Paediatric population: No specific studies of efficacy and safety are available on paediatric population.
Pharmacokinetics: The bioavailability of human hepatitis B immunoglobulin for intravenous use is complete and immediate.
IgG is quickly distributed between plasma and extravascular fluid.
Human hepatitis B immunoglobulin has a half-life of about 3-4 weeks. This half-life may vary from patient to patient.
IgG and IgG-complexes are broken down in the reticuloendothelial system.
Toxicology: Preclinical safety data: Immunoglobulins are normal constituents of the human body. The safety of VENBIG with respect to the components of the viral inactivation treatment, a well established method, has been assessed through a bibliographic review. No preclinical safety testing was therefore performed using VENBIG.

Prevention of hepatitis B virus recurrence after liver transplantation for hepatitis B virus induced liver failure in combination with antiviral therapy.
Immunoprophylaxis of hepatitis B: In case of accidental exposure in non-immunised subjects (including persons whose vaccination is incomplete or status unknown).
In haemodialysed patients, until vaccination has become effective.
In the newborn of a hepatitis B virus carrier-mother.
In subjects who did not show an immune response (no measurable hepatitis B antibodies) after vaccination and for whom a continuous prevention is necessary due to the continuous risk of being infected with hepatitis B.

Prevention of hepatitis B re-infection after liver transplantation for hepatitis B induced liver failure: In adults: 10,000 IU on the day of transplantation, peri-operatively; then 2,000-10,000 IU/day for 7 days, and as necessary to maintain antibody levels above 100-150 IU/l in HBV-DNA negative patients and above 500 IU/l in HBV-DNA positive patients.
Paediatric population: Posology must be adjusted according to body surface area, on the basis of 10,000 IU/1.73 m².
Immunoprophylaxis of hepatitis B: Prevention of hepatitis B in case of accidental exposure in non-immunised subjects: At least 500 IU, depending on the intensity of exposure, as soon as possible after exposure, and preferably within 24-72 hours.
Immunoprophylaxis of hepatitis B in haemodialysed patients: 8-12 IU/kg with a maximum of 500 IU, every 2 months until seroconversion following vaccination.
Prevention of hepatitis B in the newborn, of a hepatitis B virus carrier-mother, at birth or as soon as possible after birth: 30-100 IU/kg. In the clinical practice the intramuscular route is preferred whenever repeated administration is required to achieve seroconversion after vaccination.
In all these situations, vaccination against hepatitis B virus is highly recommended. The first vaccine dose can be injected the same day as human hepatitis B immunoglobulin, however in different sites.
In subjects who did not show an immune response (no measurable hepatitis B antibodies) after vaccination, and for whom continuous prevention is necessary, administration of 500 IU to adults and 8 IU/kg to children every 2 months can be considered; a minimum protective antibody titre is considered to be 10 mIU/mL.
Method of administration: VENBIG must be infused intravenously at an initial rate of 0.46-0.92 ml/kg/h (for example, for a patient of 65 kg at 10-20 drops/minute) for 20-30 minutes. If well tolerated, the rate of administration may gradually be increased to a maximum of 1.85 ml/kg/hr (for example, for a patient of 65 kg at 40 drops/minute) for the remainder of the infusion.
For instructions on reconstitution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.

Consequences of an overdosage are not known.

Hypersensitivity to the active substance or to any of the excipients listed in Description.
Hypersensitivity to human immunoglobulins.

Thromboembolic complications have been associated with the use of normal intravenous immunoglobulin. Therefore, caution is recommended especially for patients with thrombotic risk factors.
Patients must be monitored for serum anti-HBs antibody levels regularly.
Certain severe adverse drug reactions may be related to the rate of infusion. The recommended infusion rate given under Method of administration under Dosage & Administration must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period.
Certain adverse reactions may occur more frequently: in case of high rate of infusion; in patients with hypo- or agammaglobulinemia with or without IgA deficiency.
True hypersensitivity reactions are rare.
VENBIG contains 3.6 mg sodium (3.565 mg/ml) per ml. To be taken into consideration by patients on a controlled sodium diet, based on the total amount of product administered.
This medicinal product contains up to 92 mg sucrose (91.9 mg/ml) per ml. To be taken into consideration in patients at risk for acute renal failure.
VENBIG contains a small quantity of IgA. Individuals who are deficient in IgA have the potential for developing IgA antibodies and may have anaphylactic reactions after administration of blood components containing IgA. The physician must therefore weigh the benefit of treatment with VENBIG against the potential risk of hypersensitivity reactions.
Rarely, human hepatitis B immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who have tolerated previous treatment with immunoglobulin.
In case of renal impairment, IVIg discontinuation must be considered. While reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IVIg products containing various excipients such as sucrose, glucose and maltose, those containing sucrose as a stabiliser accounted for a disproportionate share of the total number. In patients at risk for acute renal failure or thromboembolic adverse reactions, IVIg products must be administered at the minimum rate of infusion and dose practicable.
Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the injection. In case of shock, standard medical treatment for shock must be implemented.
IVIg products can contain blood group antibodies which may act as haemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction (Coombs' test) and, rarely, haemolysis. Haemolytic anaemia may develop subsequent to IVIg therapy due to enhanced red blood (RBC) sequestration. IVIg recipients should be monitored for clinical signs and symptoms of haemolysis.
Interference with serological testing: After injection of immunoglobulin the transitory rise of the various passively transferred antibodies in the patients' blood may result in misleading positive results in serological testing.
Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D may interfere with some serological tests for red cell antibodies, for example the antiglobulin test (Coombs' test).
Transmissible agents: Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses.
Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV and for the non-enveloped viruses HAV.
The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19.
There is reassuring clinical experience regarding the lack of hepatitis A or parvovirus B19 transmission with immunoglobulins and it is also assumed that the antibody content makes an important contribution to the viral safety.
It is strongly recommended that every time that VENBIG is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
Effects on ability to drive and use machines: VENBIG has no or negligible influence on the ability to drive and use machines.
Fertility: Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.
Use in Children: No specific measures or monitoring are required.

Pregnancy: The safety of this medicinal product for use in human pregnancy has not been established in controlled clinical trials and therefore must only be given with caution to pregnant women. Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected.
Breastfeeding: The safety of VENBIG for use in human pregnancy has not been established in controlled clinical trials and therefore must only be given with caution to breastfeeding women.
Immunoglobulins are excreted into the milk and may contribute to protecting the neonate.

Summary of safety profile: Clinically significant undesirable effects with products containing human hepatitis B immunoglobulin for intravenous use may include hypersensitivity, anaphylactic shock and renal failure acute.
Other possible undesirable effects, which may occur with the use of products containing human hepatitis B immunoglobulin for intravenous use are: headache, tachycardia, hypotension, nausea, vomiting, skin reaction, erythema, itching, pruritus, arthralgia, fever, malaise and chills.
Tabulated list of adverse reactions: The table presented as follows is according to the MedDRA System Organ Classification (SOC) and Preferred Term Level (PT) and it includes undesirable effects occurring with the use of human hepatitis B immunoglobulin for intravenous use.
Frequencies have been evaluated according to the following convention: 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 the available data).
There are no robust data on the frequency of undesirable effects from clinical trials.
The following data are in line with the safety profile of human hepatitis B immunoglobulin for intravenous use, and confirmed by the post marketing experience; as the post marketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not possible to reliably estimate the frequency of these reactions. (See Table 2.)

Click on icon to see table/diagram/image

During graft re-infection preventive therapy very rare cases of intolerance reactions may be linked to an interval increase between two administrations.
For safety information with respect to transmissible agents, see Precautions.
Paediatric population: Although no specific data are avalaible on paediatric population, it is expected that frequency, nature and severity of adverse reactions do not differ between children and adults.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Live attenuated virus vaccines: Immunoglobulin administration may interfere with the development of an immune response to live attenuated virus vaccines such as rubella, mumps, measles and varicella for a period of up to 3 months.
After administration of this product, an interval of at least 3 months must elapse before vaccination with live attenuated virus vaccines.
Human hepatitis B immunoglobulin must be administrated three to four weeks after vaccination with such a live attenuated vaccine; in case administration of human hepatitis B immunoglobulin is essential within three to four weeks after vaccination, then revaccination must be performed three months after the administration of human hepatitis B immunoglobulin.
Paediatric population: No specific interaction studies have been performed in the paediatric population.

Special precautions for disposal and other handling: VENBIG must be brought to room or body temperature before use.
Total reconstitution must be obtained within 30 minutes.
Reconstitution of the solution, 500 IU vial: 1. Draw the solvent into the injection syringe.
2. Inject the solvent with the same syringe into the vial containing the lyophilised substance.
3. Shake gently until solubilisation is complete.
4. Draw the solution thus obtained into the syringe.
5. Change the needle and infuse to the patient.
The solution must be clear or slightly opalescent.
Do not use solutions that are cloudy or have deposits.
Reconstituted products must be inspected visually for particulate matter and discoloration prior to administration.
After reconstitution, the product is a clear or slightly opalescent, colourless or pale yellow liquid.
Any unused product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: This medicinal product must not be mixed with other medicinal products except the solvent mentioned in the previous text.

Do not store above 25°C.
Protect from light.
Do not freeze.
Shelf-Life: 3 years.
VENBIG must be used immediately after reconstitution.

Vaccines, Antisera & Immunologicals

J06BB04 - hepatitis B immunoglobulin ; Belongs to the class of specific immunoglobulins. Used in passive immunizations.

S