Twinrix Adult, suspension for injection

SPC Sections updated as follows:

1. NAME OF THE MEDICINAL PRODUCT Added the pharmaceutical form to the name, i.e. ‘in a pre-filled syringe’

4.2 Updated the statement regarding ‘Long-term antibody persistence data’ to confirm data is available for up to 20 years, previously 15 years and removed the statement that the anti-HAV antibodies have been predicted to persist for at least 10 years.

4.4 Added the new subheading ‘Traceability’ with the instruction to record the name and batch number of the administered product.

4.8 Updated the HPRA details for reporting adverse events.

5.1 Updated with data and information regarding long-term persistence of immune response

SPC: Change to section 4.8 – Undesirable effects – how to report a side effect
IE: Editorial change to underline website and email addresses

SPC: Change to section 6.5 – Nature and contents of container
Removed details regarding vials and the subheading regarding prefilled syringe.

SPC: Change to section 8 – Marketing authorisation number(s)
Removed the MA numbers for the Vial presentation and the subheading regarding prefilled syringe.



Section 6.6 Special precautions for disposal and other handling - Revised to improve the instructions regarding re-suspension of the vaccine following storage.
Section 4.8 Undesirable effects - Creation of a new System Organ Class for Post-marketing surveillance adverse reaction ‘General disorders and administration site conditions’, with the adverse reaction ‘Immediate injection site pain’ moved from its previous class of ‘Nervous system disorders’
Section 1 Name of the medicinal product - Removal of the dosage form ‘pre-filled syringe’ from the product name
Section 6.5 Nature and contents of container - description of vials added
Section 8 - MA numbers for vials added
Improved presentation of SPC - Minor editorial updates to SPC Sections 3, 4.2, 4.3, 4.5, 4.8 and 10

      

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Section 2: Minor format update (QRD)  and an update to include neomycin being used in the manufacturing process

 

Section 4: Minor typo update

 

Section 4.7: Minor QRD format update

 

Section 4.8: Minor QRD format update,  an update to the frequency of commonly reported adverse reactions and  an update to the adverse reporting section.

 

Section 5.3: Minor QRD format

 

Section 6.6:  Minor QRD format

 

Section 10: Update to revision date

Change to:

Section 4.4 - Special warnings and precautions for use,
Section 4.8 - Undesirable effects

4.2       Posology and method of administration

In the ‘Posology’ section, under the subheading ‘Booster dose’, updated the statement regaring the availability of long term persistence data following vaccination of up to 15 years (previously 60 months).

 

4.6       Fertility, pregnancy and lactation

Updated the heading to include ‘Fertility’

 

5.1       Pharmacodynamic properties

Updated the statement regarding two long term clinical studies conducted in adults aged 17 years to 43 years to read to reflect data for 15 years as opposed to the previous data for 60 months, to read:

In two long term clinical studies conducted in adults aged 17 years to 43 years, 56 subjects had evaluable tests 15 years after the primary vaccination with Twinrix Adult; the anti-HAV seropositivity rates were 100% in both studies and the anti-HBs seroprotection rates were 89.3% and 92.9%, respectively. The kinetics of decline of anti-HAV and anti-HBs antibodies were shown to be similar to those of the monovalent vaccines.

 

6.6       Special precautions for disposal and other handling

Updated wording regarding the description of physical appearance of the vaccine on visual inspection prior to administration, from ‘variation in physical aspect’ to ‘abnormal physical appearance’

Section 4.8 Undesirable effects

Under the subheading ‘Clinical trials’, deleted the following paragraph referring to the thiomersal-free formulation:

The current formulation of Twinrix does not contain thiomersal (an organomercuric compound) or any preservative. In a clinical study conducted with the current formulation, the incidence of pain, redness, swelling, fatigue, gastro-enteritis, headache and fever was comparable to the incidence observed with the former thiomersal and preservative containing vaccine formulation. The following undesirable effects have been reported following the widespread use of the former formulation.

 

 

 

Section 5.1 Pharmacodynamic properties

 

1.         Updated following the results of clinical studies HAB 163 and 168, i.e., the following annotations:

In a clinical study conducted in subjects over 40 years of age, the seropositivity rate for anti-HAV antibodies and seroprotection rate against hepatitis B of Twinrix Adult following a 0, 1, 6 months schedule were compared with the seropositivity and seroprotection rates of monovalent hepatitis A and B vaccines when  administered in opposite arms.

The seroprotection rate against hepatitis B after the administration of Twinrix Adult was 92% and 87.556% at 7 and 12 48 months respectively, versus 80% and 7443% after the GlaxoSmithKline Biologicals monovalent 20µg hepatitis B vaccine, and 71% and 5631% after another licensed monovalent 10µg hepatitis B vaccine. However, aAnti-HBs antibody concentrations decreased as age and body mass index increased; they were also lower in male than in female subjects.

The seropositivity rate for anti-HAV antibodies after Twinrix Adult was 97% and 96% at both 7 and 12 48 months respectively versus 99% and 9893% after the GlaxoSmithKline Biologicals monovalent hepatitis A vaccine and 99% and 97%at both 7 and 12 months after another licensed monovalent hepatitis A vaccine.

Subjects received an additional dose of the same vaccine(s) 48 months after the first dose of the primary vaccination course. One month after this dose, 95% of the subjects vaccinated with Twinrix Adult achieved seroprotective levels of anti-HBV antibodies (≥ 10 mIU/ml) and Geometric Mean Concentrations (GMC) increased by 179-fold (GMC of 7234 mIU/ml) indicative of an immune memory response.

 

In two long term clinical studies conducted in adults aged 17 years to 43 years, persistence of anti-HAV and anti-HBs antibodies has been proven up to 60 months following the initiation of a primary vaccination course of Twinrix Adult in the majority of vaccinees.  The kinetics of decline of anti-HAV and anti-HBs antibodies were shown to be similar to those of the monovalent vaccines.

 

2.         Deleted the following paragraph regarding the formulation containing thiomersal:

These data were generated with the former Twinrix formulation containing thiomersal and a preservative. A clinical study conducted with the current formulation of Twinrix in adults showed that the current formulation elicited similar seroprotection and seroconversion rates as compared to the former formulation.

 

 

4.4 Special Warnings and Precautions: Reference to Thiomersal removed, Warning regarding effect of obesity on the immune response

4.8 Undesirable effects: Revision of undesirable effects and categorisation by frequency

4.9 Overdosage: Rewording regarding cases reported during post-marketing surveillance

4.6 Pregnancy and Lactation: Clarification of use in pregnancy

5.3 Pre-clinical safety: Reference included to section 4.6

6.1 Excipients: Phenoxyethanol removed