- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
|1 dose (0.5 ml) contains:|
|Hepatitis B surface antigen 1, 2, 3||20 micrograms|
|1adjuvanted by AS04C containing:|
|- 3-O-desacyl-4'- monophosphoryl lipid A (MPL) 2||50 micrograms|
Primary immunisation:The primary immunisation consists of 4 separate 0.5 ml doses administered at the following schedule: 1 month, 2 months and 6 months from the date of the first dose. Once initiated, the primary course of vaccination at 0, 1, 2 and 6 months should be completed with Fendrix, and not with other commercially available HBV vaccine.
Booster dose:As pre-haemodialysis and haemodialysis patients are particularly exposed to HBV and have a higher risk to become chronically infected, a precautionary attitude should be considered i.e. giving a booster dose in order to ensure a protective antibody level as defined by national recommendations and guidelines. Fendrix can be used as a booster dose after a primary vaccination course with either Fendrix or any other commercial recombinant hepatitis B vaccine.
Special posology recommendation for known or presumed exposure to HBV:Data on concomitant administration of Fendrix with specific hepatitis B immunoglobulin (HBIg) have not been generated. However, in circumstances where exposure to HBV has recently occurred (e.g. stick with contaminated needle) and where simultaneous administration of Fendrix and a standard dose of HBIg is necessary, these should be given at separate injection sites.
Paediatric populationThe safety and efficacy of Fendrix in children aged less than 15 years have not been established.
Method of administrationFendrix should be injected intramuscularly in the deltoid region.
PregnancyThere are no data from the use of Fendrix in pregnant women.Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.Vaccination during pregnancy should only be performed if the risk-benefit ratio at individual level outweighs possible risks for the foetus.
Breast-feedingThere are no data from use of Fendrix during lactation. In a reproductive toxicity study in animals which included post-natal follow-up until weaning (see section 5.3), no effect on the development of the pups was observed. Vaccination should only be performed if the risk-benefit ratio at individual level outweighs possible risks for the infant.
FertilityNo fertility data are available.
Summary of the safety profileClinical trials involving the administration of 2,476 doses of Fendrix to 82 pre-haemodialysis and haemodialysis patients and to 713 healthy subjects ≥ 15 years of age allowed to document the reactogenicity of the vaccine.
Pre-haemodialysis and haemodialysis patientsThe reactogenicity profile of Fendrix in a total of 82 pre-haemodialysis and haemodialysis patients was generally comparable to that seen in healthy subjects.
List of adverse reactionsAdverse reactions reported in a clinical trial following primary vaccination with Fendrix and considered as being related or possibly related to vaccination have been categorised by frequency.Frequencies are reported as:
|Common:||(≥1/100 to <1/10)|
|Uncommon:||(≥1/1,000 to <1/100)|
|Rare:||(≥1/10,000 to <1/1,000)|
Clinical trial dataNervous system disorders:Very common: headacheGastrointestinal disorders:Common: gastrointestinal disorder
General disorders and administration site conditions:Very common: fatigue, pain Common: fever, injection site swelling, redness Unsolicited symptoms considered to be at least possibly related to vaccination were uncommonly reported and consisted of rigors, other injection site reaction and maculo-papular rash.
Healthy subjectsThe reactogenicity profile of Fendrix in healthy subjects was generally comparable to that seen in pre-haemodialysis and haemodialysis patients. In a large double-blind randomised comparative study, healthy subjects were enrolled to receive a three dose primary course of Fendrix (N= 713) or a commercially available hepatitis B vaccine (N= 238) at 0, 1, 2 months. The most common adverse reactions reported were local reactions at the injection site. Vaccination with Fendrix induced more transient local symptoms as compared to the comparator vaccine, with pain at the injection site being the most frequently reported solicited local symptom. However, solicited general symptoms were observed with similar frequencies in both groups. Adverse reactions reported in a clinical trial following primary vaccination with Fendrix and considered as being at least possibly related to vaccination have been categorised by frequency. Nervous system disorders:Common: headacheEar and labyrinth disorders:Rare: vertigoGastrointestinal disorders:Common: gastrointestinal disorderMuskuloskeletal and connective tissue disorders:Rare: tendinitis, back painInfections and infestations:Rare: viral infection
General disorders and administration site conditions:Very common: injection site swelling, fatigue, pain, rednessCommon: feverUncommon: other injection site reactionRare: rigors, hot flushes, thirst, astheniaImmune system disorders:Rare: allergyPsychiatric disorders:Rare: nervousnessNo increase in the incidence or severity of these adverse reactions was seen with subsequent doses of the primary vaccination schedule. No increase in the reactogenicity was observed after the booster vaccination with respect to the primary vaccination. • Experience with hepatitis B vaccine:Following widespread use of hepatitis B vaccines, in very rare cases, syncope, paralysis, neuropathy, neuritis (including Guillain-Barré syndrome, optic neuritis and multiple sclerosis), encephalitis, encephalopathy, meningitis and convulsions have been reported. The causal relationship to the vaccine has not been established.Anaphylaxis, allergic reactions including anaphylactoid reactions and mimicking serum sickness have also been reported very rarely with hepatitis B vaccines.
Reporting of suspected adverse reactionsReporting 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.
Immunological dataIn pre-haemodialysis and haemodialysis patients:In a comparative clinical study in 165 pre-haemodialysis and haemodialysis patients (15 years and above), protective levels of specific humoral antibodies (anti-HBs titres ≥ 10 mIU/ml) were observed in 74.4% of Fendrix recipients (N = 82) one month after the third dose (i.e at month 3), as compared to 52.4% of patients in the control group who received a double dose of a commercially available hepatitis B vaccine (N = 83) for this population.At month 3, Geometric Mean Titres (GMT) were 223.0 mIU/ml and 50.1 mIU/ml in the Fendrix and control groups respectively, with 41.0% and 15.9% of subjects with anti-HBs antibody titres ≥100 mIU/ml respectively.After completion of a four dose primary course (i.e at month 7), 90.9% of Fendrix recipients were seroprotected (≥ 10 mIU/ml) against hepatitis B, in comparison with 84.4% in a control group who received the commercially available hepatitis B vaccine.At month 7, GMTs were 3559.2 mIU/ml and 933.0 mIU/ml in the Fendrix and control groups who received the commercially available hepatitis B vaccine respectively, with 83.1% and 67.5% of subjects with anti-HBs antibody titres ≥100 mIU/ml respectively.
In pre-haemodialysis and haemodialysis patients:Anti-HBs antibodies have been shown to persist for at least 36 months following a 0, 1, 2, 6 month primary course of Fendrix in pre-haemodialysis and haemodialysis patients. At month 36, 80.4% of these patients retained protective antibody levels (anti-HBs titres ≥ 10mIU/ml), as compared to 51.3% of patients who received a commercially available hepatitis B vaccine.At month 36, GMTs were 154.1 mIU/ml and 111.9 mIU/ml in the Fendrix and control groups respectively, with 58.7% and 38.5% of subjects with anti-HBs antibody titres ≥100 mIU/ml respectively.
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