Ambirix is indicated in non-immune children and adolescents from 1 year up to and including 15 years of age for protection against hepatitis A and hepatitis B infection. Protection against hepatitis B infections may not be obtained until after the second dose (see section 5.1). Therefore: • Ambirix should be used only when there is a relatively low risk of hepatitis B infection during the vaccination course. • It is recommended that Ambirix should be administered in settings where completion of the two-dose vaccination course can be assured.

Dosage A dose of 1.0 ml is recommended for subjects from 1 year up to and including 15 years of age. • Primary vaccination schedule The standard primary course of vaccination consists of two doses, the first administered at the elected date and the second between 6 and 12 months after the first dose. The recommended schedule should be adhered to. Once initiated, the primary course of vaccination should be completed with the same vaccine. • Booster dose In situations where a booster dose of hepatitis A and/or hepatitis B is desired, a monovalent or combined vaccine can be given. The safety and immunogenicity of Ambirix administered as a booster dose following a two dose primary course have not been evaluated. Long-term antibody persistence data following vaccination with Ambirix are available up to 15 years after vaccination (see section 5.1). The anti-hepatitis B surface antigen (anti-HBs) and anti-hepatitis A virus (anti-HAV) antibody titres observed following a primary vaccination course with Ambirix are in the range of what is seen following vaccination with the monovalent hepatitis A and B vaccines. General guidelines for booster vaccination can therefore be drawn from experience with the monovalent vaccines, as follows. Hepatitis B The need for a booster dose of hepatitis B vaccine in healthy individuals who have received a full primary vaccination course has not been established. However some official vaccination programmes currently include a recommendation for a booster dose of hepatitis B vaccine and these should be respected. For some categories of subjects at risk of exposure to HBV (e.g. haemodialysis or immunocompromised patients) a precautionary attitude should be considered to ensure that a protective antibody level = 10 mIU/ml is maintained. Hepatitis A It is not yet fully established whether immunocompetent individuals who have responded to hepatitis A vaccination will require booster doses as protection in the absence of detectable antibodies may be ensured by immunological memory. Guidelines for boosting are based on the assumption that antibodies are required for protection. Paediatric population The safety and efficacy of Ambirix in children aged less than 1 year have not been established. No data are available. Method of administration Ambirix is for intramuscular injection, usually into the deltoid muscle. However the anterolateral thigh may be used in very young subjects if preferred. Exceptionally, the vaccine may be administered subcutaneously in patients with thrombocytopenia or bleeding disorders. However, this route of administration may result in suboptimal immune response to the vaccine (see section 4.4).

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or neomycin. Hypersensitivity after previous administration of hepatitis A and/or hepatitis B vaccines. As with other vaccines, the administration of Ambirix should be postponed in subjects suffering from acute severe febrile illness.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic reactions following the administration of the vaccine. Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints. It is possible that subjects may be in the incubation period of a hepatitis A or hepatitis B infection at the time of vaccination. It is not known whether Ambirix will prevent hepatitis A and hepatitis B in such cases. The vaccine will not prevent infection caused by other agents such as hepatitis C and hepatitis E and other pathogens known to infect the liver. Ambirix is not recommended for postexposure prophylaxis (e.g. needle stick injury). If rapid protection against hepatitis B is required, the standard three-dose regimen of the combined vaccine containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of recombinant hepatitis B surface antigen is recommended. This is because, a higher proportion of subjects are protected in the interval between the second and third dose of the three-dose combined vaccine, than after a single dose of Ambirix. This difference is no longer present after the second dose of Ambirix (see section 5.1 for seroprotection rates). It is recommended that the two-dose regimen of Ambirix be completed prior to start of sexual activity. The vaccine has not been tested in patients with an impaired immune system. In haemodialysis patients and persons with an impaired immune system, adequate anti-HAV and anti-HBs antibody titers may not be obtained after the primary immunisation course. Since intradermal injection or intramuscular administration into the gluteal muscle could lead to a suboptimal response to the vaccine, these routes should be avoided. However, exceptionally Ambirix can be administered subcutaneously to subjects with thrombocytopenia or bleeding disorders since bleeding may occur following an intramuscular administration to these subjects. Ambirix should under no circumstances be administered intravascularly. This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

No data on concomitant administration of Ambirix with specific hepatitis A immunoglobulin or hepatitis B immunoglobulin have been generated. However, when the monovalent hepatitis A and hepatitis B vaccines were administered concomitantly with specific immunoglobulins there was no effect on seroconversion rates. Concomitant immunoglobulin administration may result in lower antibody titres. When Ambirix was administered concomitantly with, but as a separate injection to a combined diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b vaccine (DTPa-IPV+Hib) or with a combined Measles-Mumps-Rubella vaccine in the second year of life, immune responses to all antigens were satisfactory (see section 5.1). Concomitant administration of Ambirix and other vaccines than those listed above has not been studied. It is advised that Ambirix should not be administered at the same time as other vaccines unless absolutely necessary. Concomitant vaccines should always be administered at separate injection sites and preferably into different limbs. It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate response may not be achieved.

Pregnancy Ambirix can be used during pregnancy only when clearly needed, and the possible advantages outweigh the potential risks for the foetus. Breast-feeding Ambirix should only be used during breast-feeding when the possible advantages outweigh the potential risks. Fertility No fertility data are available.

Ambirix has no or negligible influence on the ability to drive and use machines.

Summary of safety profile Clinical trials involved the administration of 2029 doses of Ambirix to 1027 subjects from 1 year up to and including 15 years of age. In 2 comparative trials in subjects aged 1-15 years, the incidences of local and general solicited symptoms after a two-dose regimen of Ambirix was overall similar to that seen with the three-dose combined vaccine containing 360 ELISA Units of HAV and 10 µg of HBsAg. The most commonly reported adverse reactions following Ambirix administration are pain and fatigue occurring in an approximated per dose frequency of 50% and 30% respectively. List of adverse reactions Local and general adverse reactions reported following primary vaccination with Ambirix were categorised by frequency. Adverse reactions reported are listed according to the following frequency: 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 The following adverse reactions were reported during clinical trials with Ambirix. • Clinical trial data Metabolism and nutrition disorders Very common: appetite lost Psychiatric disorders Very common: irritability Nervous system disorders Very common: headache Common: drowsiness Gastrointestinal disorders Common: gastrointestinal symptoms General disorders and administration site conditions Very common: fatigue, pain and redness at the injection site Common: fever, swelling at the injection site In addition, the following adverse reactions were reported during clinical trials with GlaxoSmithKline’s other combined hepatitis A and hepatitis B vaccines (given as a 3 or 4 dose schedule). Infections and infestations Uncommon: upper respiratory tract infection Blood and lymphatic system disorders Rare: lymphadenopathy Nervous system disorders Uncommon: dizziness Rare: paraesthesia Vascular disorders Rare: hypotension Gastrointestinal disorders Common: diarrhoea, nausea Uncommon: vomiting, abdominal pain* Skin and subcutaneous tissue disorders Rare: pruritus, rash Very rare: urticaria Musculoskeletal and connective tissue disorders Uncommon: myalgia Rare: arthralgia General disorders and administration site conditions Common: malaise, injection site reaction Rare: chills, influenza like illness * refers to adverse reactions observed in clinical trials performed with the paediatric formulation • Post-marketing data Because these events were reported spontaneously, it is not possible to reliably estimate their frequency. The following adverse reactions were reported during post-marketing surveillance following vaccination with Ambirix. Immune system disorders Allergic reactions including anaphylactic and anaphylactoid reactions Nervous system disorders Syncope or vasovagal responses to injection, localised hypoaesthesia Following widespread use of either GlaxoSmithKline’s combined hepatitis A and hepatitis B vaccines or the monovalent hepatitis A and/or hepatitis B vaccines, the following adverse reactions have additionally been reported. Infections and infestations Meningitis Blood and lymphatic system disorders Thrombocytopenic purpura, thrombocytopenia Immune system disorders Allergic reactions including mimicking serum sickness, angioneurotic oedema Nervous system disorders Multiple sclerosis, encephalitis, encephalopathy, polyneuritis such as Guillain- Barré syndrome (with ascending paralysis), myelitis, convulsions, paralysis, facial palsy, neuritis, optic neuritis, neuropathy Vascular disorders Vasculitis Hepatobiliary disorders Abnormal liver function tests Skin and subcutaneous tissue disorders Erythema multiforme, lichen planus Musculoskeletal and connective tissue disorders Arthritis, muscular weakness General disorders and administration site conditions Immediate injection site pain, stinging and burning sensation 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Cases of with GlaxoSmithKline’s combined hepatitis A and hepatitis B vaccine have been reported during post-marketing surveillance. Adverse reactions reported following overdosage were similar to those reported with normal vaccine administration.

Pharmaco therapeutic group: Vaccines, Hepatitis vaccines, ATC code J07BC20. Mechanism of action Ambirix confers immunity against HAV and HBV infection by inducing specific anti-HAV and anti-HBs antibodies. Clinical studies Immune responses post-primary vaccination In clinical studies involving subjects from 1 year up to and including 15 years old, seropositivity rates for anti-HAV antibodies were 99.1% one month after the first dose and 100% after the second dose given at month 6 (i.e month 7). Seropositivity rates for anti-HBs antibodies were 74.2% one month after the first dose and 100% after the second dose given at month 6 (i.e. month 7). The anti-HBs seroprotection rates (titers = 10 mlU/ml) at these time points were 37.4% and 98.2% respectively. In a comparative clinical trial conducted among subjects aged from 12 years up to and including 15 years of age, 142 received two doses of Ambirix and 147 received the standard three-dose (0, 1, 6 months) of the combined HAB vaccine. The latter contained 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of recombinant hepatitis B surface antigen. For the 289 subjects evaluable for immunogenicity, seroprotection rates (SP in the table below) against hepatitis B were significantly higher at months 2 and 6 with the three-dose vaccine than with Ambirix. The immune response elicited by Ambirix at month 7 (i.e. after completion of the vaccination course) was non-inferior to that to the three-dose vaccine. Vaccine group Anti-HBs Month 2 SP (%) Anti-HBs Month 6 SP (%) Anti-HBs Month 7 SP (%) Ambirix 38 68.3 97.9 Combined HAB vaccine (360/10)* 85.6 98.0 100 * containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of recombinant hepatitis B surface antigen Immune responses obtained one month after the full vaccination course (i.e at month 7) in a comparative clinical trial in children aged 1-11 years are presented in the following table. Also shown are the results reported in the comparative study performed in 12-15 year-olds. In both studies, subjects received either a two-dose schedule of Ambirix or a three-dose regimen of the combined HAB vaccine (360/10) containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of recombinant hepatitis B surface antigen. Anti-HAV Anti-HBs Age group Vaccine group N S+ (%) N SP (%) Ambirix 98 100 98 98 1-5 yrs old Combined HAB vaccine (360/10)* 92 100 92 100 Ambirix 103 100 103 99 6-11 yrs old Combined HAB vaccine (360/10)* 96 100 96 100 Ambirix 142 100 142 97.9 12-15 yrs old Combined HAB vaccine (360/10)* 147 100 147 100 * containing 360 ELISA Units of formalin inactivated hepatitis A virus and 10 micrograms of recombinant hepatitis B surface antigen Immune response post-primary vaccination using 0-12 month schedule In a clinical study, 102 subjects aged from 12 years up to and including 15 years received the second dose of Ambirix at month 12. Seropositivity rates for anti-HAV were 99.0% and seropositivity rates for anti-HBs were 99.0% at month 13 with seroprotection rates of 97.0%. Persistence of immune responses The persistence of immune responses was evaluated in children up to 15 years after primary vaccination with Ambirix and is presented in the Table below. Anti-HAV Anti-HBs Year after the first vaccine dose Age at primary vaccination Schedule (Month) S+ (%) SP (%) 0, 6 100 84.8 6 12-15 yrs old 0, 12 100 92.9 10 1-11 yrs old 0, 6 100 77.3 15 12-15 yrs old 0, 6 100 81.1 After 15 years in subjects aged 12-15 years at primary vaccination the anti- HAV and anti-HBs antibody concentrations were comparable between groups that had received Ambirix or a 3-dose regimen of the combined HAB vaccine (360/10). In the Ambirix group, a challenge dose of a HBV vaccine was given to a limited number of subjects (n=8) whose anti-HBs antibody concentrations decreased to < 10 mIU/ml and all mounted an anamnestic response. Concomitant vaccinations When the first dose of Ambirix was administered concomitantly with a booster dose of a combined diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b vaccine (DTPa-IPV+Hib) or with the first dose of a combined Measles-Mumps-Rubella vaccine in the second year of life, immune responses to all antigens were satisfactory.

Not applicable.

Non-clinical data reveal no special hazard for humans based on general safety studies.

Sodium chloride Water for injections For adjuvants, see section 2.

Not applicable.

3 years.

Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original package, in order to protect from light.

1 ml of suspension in a pre-filled syringe (type I glass) with a plunger stopper (butyl rubber) and with a rubber tip cap. The tip cap and rubber plunger stopper of the pre-filled syringe are made with synthetic rubber. Pack sizes of 1, 10 and 50, with or without needles. Not all pack sizes may be marketed.

and other handling Upon storage, a fine white deposit with a clear colourless layer above may be observed. The vaccine should be re-suspended before use. When re-suspended, the vaccine will have a uniform hazy white appearance. Re-suspension of the vaccine to obtain a uniform hazy white suspension The vaccine should be re-suspended following the steps below. 1. Hold the syringe upright in a closed hand. 2. Shake the syringe by tipping it upside down and back again. 3. Repeat this action vigorously for at least 15 seconds. 4. Inspect the vaccine again: a. If the vaccine appears as a uniform hazy white suspension, it is ready to use – the appearance should not be clear. b. If the vaccine still does not appear as a uniform hazy white suspension - tip upside down and back again for at least another 15 seconds - then inspect again. The vaccine should be inspected visually for any foreign particulate matter and/or abnormal physical appearance prior to administration. In the event of either being observed, do not administer the vaccine. Instructions for the pre-filled syringe after re-suspension Hold the syringe by the barrel, not by the plunger. Unscrew the syringe cap by twisting it anticlockwise. To attach the needle, connect the hub to the Luer Lock Adaptor and rotate a quarter turn clockwise until you feel it lock. Do not pull the syringe plunger out of the barrel. If it happens, do not administer the vaccine. Disposal Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Plunger Barrel Cap Luer Lock Adaptor Needle hub

Feb. 5, 2026

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